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Biomedical subjects

M Cardillo

Publications and source records attributed to M Cardillo.

At least 19 recordsLinked to original sources
PubMed2005

Mycophenolate mofetil pharmacokinetic monitoring in pediatric kidney transplant recipients.

This open-label, longitudinal, long-term study of de novo pediatric renal transplant recipients was designed to investigate the pharmacokinetics (PK) of mycophenolic acid (MPA) and its possible interaction with cyclosporine (CsA). Thirty-four children on an immunosuppressive regimen of CsA, prednisone, and mycophenolate mofetil (MMF, 300-400 mg/m2 twice daily) were investigated at 6, 30, 180, and 360 days after transplantation. Considerable interindividual variability in the areas under the concentration curve (AUC(0-12)) of MPA was observed during the follow-up, although the dose of MMF remained the same over the same time. Predose levels (C0) increased significantly during the first 6 months after transplantation: C0 at 6 and 180 days after transplantation was 0.8 +/- 0.6 and 1.9 +/- 1.1 microg/mL (P < .0001). A significant time-dependent increase in the AUC of MPA was also observed during the first 6 posttransplant months: AUC(0-12) at 6 and 180 days after transplantation was 23.3 +/- 10.8 and 40 +/- 11.6 mg*h/L (P = .003). MPA concentrations 3 and 4 hours after MMF intake were the individual time points that best correlated with the full MPA AUC (r = 0.8 and 0.79; P < .001). The abbreviated MPA AUC (0-4 hours) correlated reasonably with the full AUC (r = 0.87; P < .001). Finally, a significant reduction in CsA dose during the first 6 posttransplant months (P < .001) matched the significant increases in both MPA C0 and full MPA AUC, thus demonstrating the interaction of the 2 immunosuppressive drugs. These observations suggest the need for therapeutic drug monitoring when adjusting the dose of MMF in children.

Child↗
PubMed2003

Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches.

BACKGROUND: Although a growing body of literature regarding polyoma BK virus (BKV) infection and associated interstitial nephritis in kidney-allograft recipients is becoming available, the impact of BKV infection in the pediatric population has not been fully evaluated. METHODS: In a retrospective analysis, we performed polymerase chain reaction (PCR) assays for BKV DNA in serum and urine samples from 100 pediatric kidney-allograft recipients referred to our institution in the last 5 years. RESULTS: BKV viruria was observed in 26 of 100 patients, whereas BKV viremia was demonstrated in 5 patients. Serum creatinine was significantly higher in recipients with positive BK viremia compared with BKV DNA-negative patients (mean 2.66 vs. 1.14 mg/100 mL). Renal biopsy performed in 3 of 5 patients showed graft damage consistent with interstitial nephropathy. In the univariate analysis, negative antibody status of the recipient and the presence of mycophenolate mofetil in baseline immunosuppression were the two factors predictive of active BKV infection. CONCLUSIONS: Our study shows that BKV-associated nephropathy is a relevant complication in the pediatric kidney transplantation setting also. Identification of patients at risk of developing virus-associated nephropathy, through prospective quantification of viral load, could improve clinical outcome by allowing the use of timely preemptive therapy guided by BKV DNA levels.

Adolescent↗
PubMed2003

Geographic range size, life history and rates of diversification in Australian mammals.

What causes species richness to vary among different groups of organisms? Two hypotheses are that large geographical ranges and fast life history either reduce extinction rates or raise speciation rates, elevating a clade's rate of diversification. Here we present a comparative analysis of these hypotheses using data on the phylogenetic relationships, geographical ranges and life history of the terrestrial mammal fauna of Australia. By comparing species richness patterns to null models, we show that species are distributed nonrandomly among genera. Using sister-clade comparisons to control for clade age, we then find that faster diversification is significantly associated with larger geographical ranges and larger litters, but there is no evidence for an effect of body size or age at first breeding on diversification rates. We believe the most likely explanation for these patterns is that larger litters and geographical ranges increase diversification rates because they buffer species from extinction. We also discuss the possibility that positive effects of litter size and range size on diversification rates result from elevated speciation rates.

Animals↗
PubMed2003

Testing the link between the latitudinal gradient in species richness and rates of molecular evolution.

Numerous hypotheses have been proposed to explain latitudinal gradients in species richness, but all are subject to ongoing debate. Here we examine Rohde's (1978, 1992) hypothesis, which proposes that climatic conditions at low latitudes lead to elevated rates of speciation. This hypothesis predicts that rates of molecular evolution should increase towards lower latitudes, but this prediction has never been tested. We discuss potential links between rates of molecular evolution and latitudinal diversity gradients, and present the first test of latitudinal variation in rates of molecular evolution. Using 45 phylogenetically independent, latitudinally separated pairs of bird species and higher taxa, we compare rates of evolution of two mitochondrial genes and DNA-DNA hybridization distances. We find no support for an effect of latitude on rate of molecular evolution. This result casts doubt on the generality of a key component of Rohde's hypothesis linking climate and speciation.

Animals↗
PubMed2002

High frequency of anti-endomysial reactivity in candidates to heart transplant.

BACKGROUND: A possible link between coeliac disease and dilated cardiomyopathy has recently been suggested. AIMS: . To assess the frequency of anti-endomysial antibodies, the marker for coeliac disease, in patients with different forms of heart failure, and to establish the clinical features of those endomysial antibody positive. SUBJECTS AND METHODS: . A total of 642 consecutive patients entering the waiting list for heart transplantation from 1995 through 1997 were studied. The prevalence of endomysial IgA antibodies, determined by indirect immunofluorescence, was compared to that observed in three surveys conducted in the Italian general population. RESULTS: Of the 642 patients, 12 (1.9%; 95% confidence interval 0.97-3.2) resulted endomysial antibody positive, versus 34/9,720 healthy controls (0.35%; 95% confidence interval, 0.23-0.47), accounting for a relative risk of 5.3 (95% confidence interval, 2.8-10.3). Anti-endomysial antibodies were found in 6/275 patients with dilated cardiomyopathy and 6/367 with other forms of heart failure (2.2% versus 1.6%; 95% confidence interval 0.8-4.7 and 0.6-3.5), with no statistical difference. The 12 endomysial antibody positive patients were leaner (body mass index, 22.0 +/- 1.9 vs 24.2 +/- 3. 1, p<0. 05) than 36 seronegative patients matched for baseline demographics and aetiology of cardiomyopathy No differences were observed as regards clinical, biochemical and echocardiographic features, mortality in waiting list and 2-year post-transplant survival. CONCLUSIONS: Patients with end-stage heart failure are at increased risk for coeliac disease as compared to the general population.

Adult↗
PubMed2001

Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases.

BACKGROUND: Epithelioid sarcoma is a rare tumor with characteristic morphologic and immunohistochemical features. It can be confused histologically and cytologically with a variety of benign and malignant lesions, including a granulomatous process, synovial sarcoma, melanoma, squamous cell carcinoma, and adenocarcinoma. The objective of this study was to define the cytologic features of this rare tumor. METHODS: The cytologic features of nine histologically confirmed epithelioid sarcomas were analyzed. The criteria evaluated included cell size and shape, cell borders, cluster organization, cytoplasmic characteristics, nuclear and nucleolar features, and background characteristics. RESULTS: In most cases, single, dispersed cells represented the predominant pattern, with only a few small clusters present. The cells were mostly round with interspersed spindle cells and mild to moderate pleomorphism. The nuclei were large and eccentrically located, with a plasmacytoid appearance. A pale zone in the perinuclear area was evident in three of nine cases. Well-defined cell borders with intercellular spaces between malignant cells were observed in eight cases. In three cases, a granuloma-like structure was identified. In two cases, the cells were mostly spindle and showed greater cellular pleomorphism. CONCLUSION: Epithelioid sarcoma is an uncommon tumor with a wide range of differential diagnoses, especially in cytology specimens. Awareness of its existence and knowledge of its cytologic features are important for a correct diagnosis.

Adult↗
PubMed2001

CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus.

BACKGROUND: Recent studies have reported an increased incidence of squamous intraepithelial lesions in women infected with the human immunodeficiency virus (HIV). However, to the authors' knowledge there are scarce data regarding the relation between the CD4 T-lymphocyte count (CD4+), HIV viral load, and the development of cervical dysplasia as evidenced by cervicovaginal cytology. The objective of the current study was to examine the association between cervicovaginal smears (with and without squamous lesions) from HIV-infected women and their CD4+ counts and HIV viral load. METHODS: Two hundred ninety-six cervicovaginal smears from 108 HIV-infected women were reviewed and classified according to the Bethesda system. Abnormal cytologies (n = 74) were followed by colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the time of the cytologic evaluation. Statistical analysis was performed using the Student t test and the Mann-Whitney U test. RESULTS: The control group (n = 222) had significantly higher CD4+ counts (378 vs. 246 cells/microL; P < 0.001) compared with the group with cervical lesions. There was no apparent difference between the CD4+ counts from women with low grade lesions and those from women with high grade lesions. The HIV viral load was significantly higher in patients with cytologic abnormalities than in those with negative Papanicolaou smears (P = 0.006). CONCLUSIONS: The degree of immunosuppression may contribute to the development of intraepithelial lesions in HIV-positive women, but once the lesion is established disease progression may not be affected by the CD4+ counts.

Adolescent↗
PubMed2001

Successful renal transplantation in children under 6 years of age.

To evaluate the efficacy of renal transplantation in small pediatric patients, we have reviewed 41 allografts performed in 39 children (28 M/11 F) less than 6 years of age between 1987 and 1998 in the North Italy Transplant Program. Of these patients, 39 had a cadaver donor and 2 a living-related donor, with ages ranging from 20 days to 35 years. The mean follow-up was 56 months. Graft survival was 74.5% and 70.5% at 1 and 5 years, respectively. The causes of graft lost were acute rejection (4), graft vascular thrombosis (4), and hemolytic uremic syndrome recurrence (1). Only 1 patient has died due to chickenpox. Double and triple immunosuppressive therapies were used in 63% and 37% of patients, respectively, on the basis of different center protocols, without differences in graft survival. Steroids were successfully administered on alternate days in 37% of patients, 6-12 months after transplantation. Thrombosis was reported in 2 of 6 kidneys from donors less than 1 year of age and in 2 of 35 donors older than 1 year (P < 0.05). Thirty rejections occurred in 23 patients: 7 episodes were steroid resistant and were treated with ATG/OKT3. Thirty-four infections were reported in 16 of 41 patients; of these 17 were viral, 14 bacterial, and 3 due to Mycoplasma. Four surgical complications were reported: 1 graft artery stenosis, 1 ureteral stenosis, 1 urinary leak, and 1 lymphocele. Mean height standard deviation score improved from -2.0 +/- 1.3 pre transplantation to -1.8 +/- 1.4, -1.5 +/- 1.3, and -1.5 +/- 1.5 at 1, 2, and 5 years post transplantation. Linear growth was significantly better in infants treated with alternate-day steroids. Hypertension was a frequent complication, since 19 of the 30 patients with a 5-year follow-up were still being treated with antihypertensive drugs. In conclusion, graft survival in patients less than 6 years old is satisfactory and similar to that obtained in children aged from 6 to 18 years (70.5% vs. 78.9% at 5 years, P = NS). Consequently, since there are many difficulties in managing infants on maintenance dialysis, an early transplant should be considered. Donors older than 24 months carry a low risk of vascular thrombosis and may be successfully grafted in infants.

Child Development↗
PubMed2000

Split liver is an effective tool to transplant paediatric patients.

Transplantation activity is dependent upon organ procurement; although great efforts are made to enlarge the cadaver donors' pool, it still remains far too small to meet the recipients' need. Waiting time is a particular problem for paediatric patients, and mortality on the waiting list for liver transplantation is very high. The number of paediatric donors is far too small to satisfy the request. To enlarge the liver pool, the split-liver procedure was introduced in several Transplant Centers. In November 1997, the North Italy Transplant program (NITp) Working Group for Liver Transplantation decided to start an official Split-liver Program. A protocol was therefore defined and criteria for donor's and recipient's eligibility were established to minimize the risk. The Working Group also standardized the technical procedure and defined collaboration between centers. Out of 410 cadaver liver donors used in the NITp, from 1 November 1997 until 31 May 1999, 49 patients (37 males and 12 females) were chosen for the split-liver procedure. Mean age was 29.9 +/- 17.5 years. Mean ICU stay of the donors was considerably short (2.5 +/- 2.1 days), and the other conditions foreseen for donor eligibility were met. In all cases (except two) an "in situ" technique was performed. Forty-nine adult recipients and 43 children were transplanted by the split-liver technique in our Transplant Centers. One right lobe and five left liver lobes were sent to Transplant Centers outside the NITp. Adult recipient age ranged from 18 to 60 years (mean 46.4 +/- 11.7 years), and the paediatric one from 2 to 144 months (mean 24.8). Mean patient follow-up was 8.3 +/- 5.5 months. In the paediatric group, the graft was successful in 34 cases (79%), five patients (10.2%) died and four (9.3%) were re-transplanted. In the adult group, graft survival was 67.3%, 11 (22%) patients died and 5 (10%) were re-transplanted. On 1 November 1997, 30 paediatric patients were on the liver waiting list. In the preceding 19 months, 52 patients were newly enrolled, and 36 transplants were performed. The mean waiting time of paediatric patients was 259 days (range 1-919 says). From 1 November 1997 to 31 May 1999, 61 paediatric patients were newly enrolled. In this period 70 patients were transplanted. The mean waiting time was 185 days (1-1010 days). At present, the liver waiting list includes eight paediatric patients. Split-liver transplantation is a successful procedure, effective in reducing waiting time for paediatric patients. It should be established if this may be a tool to enlarge the organ pool also for adult liver transplantation.

Adolescent↗
PubMed2000

An algorithm for cadaver kidney allocation based on a multivariate analysis of factors impacting on cadaver kidney graft survival and function.

The large imbalance between cadaver kidney supply and demand makes the implementation of equitable and effective organ allocation systems an urgent need. This has triggered a revision of the criteria used so far for cadaver kidney allocation within the North Italy Transplant program, not least in the light of the many changes that have occurred recently with respect to broader criteria for admission of patients to the waiting list, donor selection, tissue-typing methods, organ preservation and immunosuppressive protocols. We based the critical revision of our cadaver kidney allocation algorithm on univariate and multivariate analysis of a number of immunological, clinical, social and administrative factors that impacted on the transplant outcome in 2,917 patients transplanted in the 12 transplant centers operating within our organization from 1 January 1990 to 30 September 1997. This analysis indicated that younger donor age, absence of pretransplant transfusions, patient dialysis center and level of HLA match showed statistically significant positive associations with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. The results of this analysis were used to develop a new computer-assisted version of our adult kidney allocation algorithm. It works in two steps (local pool first, then the entire waiting list) and four levels (0-1 HLA MM, PRA+; 2 HLA MM, PRA+; 0-1 MM, PRA-; 2-4 HLA MM, PRA-); within each level, selection takes into account waiting time and age difference from donor age. The evaluation of 731 transplants allocated in 19 months with the new algorithm, as against 698 transplants allocated in the preceding 19 months according to the previous algorithm, showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.2% versus 22.6%). The use of the new algorithm was also associated with a significantly increased number of transplanted alloimmunized patients (18.8% versus 9.2% with the previous algorithm) and recipients with 0-1 HLA mismatches (22% versus 14.3%). Furthermore, the number of kidneys used locally has steadily increased. Differences in 6-month graft survival and percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with the new versus the previous algorithm. Survivals were 93.7% versus 91.8%. Percentages of patients with excellent renal function were 69.9% and 71.8%, respectively. These preliminary data suggest that the new algorithm improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6-month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.

Adult↗
PubMed2000

De novo cancers in paediatric renal transplant recipients: a multicentre analysis within the North Italy Transplant programme (NITp), Italy.

The purpose of this study was to determine the frequency and the outcome of de novo malignancies in a cohort of renal transplant paediatric patients. The records of 493 kidney transplants, carried out in 454 paediatric recipients at the three paediatric transplant centres of the North Italy Transplant programme (NITp, Italy) were reviewed. 10 cases of malignancies (2.2%) comprising both PTLD (post-transplant lymphoproliferative disorders) (6 cases, 1.3%) and non-PTLD malignancies (4 cases, 0.88%) were reported. Non-PTLD included one urothelial carcinoma and one Wilms' tumour of the recipient's left native kidney, one abdominal dysgerminoma and one optic nerve glioma of the left eye. The PTLD consisted of localised or disseminated Epstein-Barr virus (EBV)--associated B-lymphocyte monoclonal (5 cases) and polyclonal (1 case) proliferations. All patients suffering from PTLD had been EBV-negative at the time of transplantation, but developed EBV primary infection after transplantation. All PTLD patient donors were EBV-positive. In addition, all but 1 patient received, before and/or after transplantation, a range of immunosuppressive drugs in addition to the baseline prophylactic immunosuppressive regimen. Moreover, 3 patients suffered from syndromes associated with a genetic predisposition to cancer. Finally, the malignancies reported here were associated with 20% graft failure and 20% mortality rates.

Adolescent↗
PubMed2000

[Systemic and pulmonary vascular resistance in brain death].

BACKGROUND: Hemodynamic instability is known to affect brain dead subjects and it can be dangerous for the viability of transplantable organs. Aim of the present study was to assess the hemodynamic performance in brain dead subjects, the changes during the legal observation period and the results of therapeutic management. METHODS: The authors evaluated 28 consecutive adult brain dead subjects, all in intensive treatment, controlled ventilation, infusion therapy and/or dopamine administration and continuous direct monitoring of arterial pressure. Ten hemodynamic parameters have been registered by the thermodilution method and the Swann-Ganz catheter. The Legal Committee performed measurements at the beginning (T0) and the end (T6) of the observation period, which lasts 6 hours according to the current law on death certification (Law N. 578/93). RESULTS: Low systemic and pulmonary vascular resistances have been documented in the majority of subjects (75%), both treated only with fluids and with the additional dopamine administration (dosage lower than 10 ug/Kg/min). The above-mentioned reduction was similar at the two different monitored times (T0 and T6). CONCLUSIONS: This situation can be ascribed to the destruction of the cerebral vasoactive centers and the consequent hypotension is due to autonomic nervous system dysfunction. Hemodynamic instability must be treated by fluids and inotropic drugs, but they may cause cardiac and respiratory problems, thus it is suggested to use also low doses of vasoconstrictive drugs, provided that cardiac condition allows this therapeutic strategy.

Adolescent↗
PubMed2000

[Organ transplantation: results and perspectives].

Nowadays organ transplantation is a life-saving procedure, or anyhow it can considerably improve the life quality of patients suffering from irreversible organ impairment. Monitoring transplantation outcome is the last step of a long process that starts with cadaver donor identification, selection and clinical management, and continues with organ allocation, patient evaluation, surgical operation and clinical follow-up. The National Transplantation Committee has been discussing many of these items and, in 1995, it set up two protocols, one on liver exchange for urgent patients and the other on transplantation in the pediatric patient. The protocols application has met many difficulties, mainly due to the uneven behaviours of the different inter-regional organizations. In this paper we comment on the two main aspects to be submitted to the next National Committee: organ allocation and transplantation outcome. As far as the last point is concerned, the enclosed data are based on the experience of the North Italy Transplant program (NITp), and on that of the major international registries. Without any doubt these data demontrate that organ transplantation is to be ascribed among the successes of medicine in the just closed century.

Humans↗
PubMed1999

Developmental expression of voltage-gated potassium channel beta subunits.

Expression of potassium channel beta subunits (Kvbeta) was determined in the developing mouse CNS using an antiserum against an amino acid sequence present in the C-terminus of Kvbeta1, Kvbeta2, and Kvbeta3. Using the anti-Kvbeta antiserum, we determined that Kvbeta expression is restricted to the spinal cord and dorsal root ganglia in the embryonic CNS. At birth, Kvbeta expression is detected in brainstem and midbrain nuclei, but was not detected in the hippocampus, cerebellum or cerebral cortex. During the first postnatal week, Kvbeta expression is present in hippocampal and cortical pyramidal cells and in cerebellar Purkinje cells. Expression of Kvbeta subunits reaches adult levels by the third postnatal week in all of the brain regions examined. A rabbit antiserum directed against a unique peptide sequence in the N-terminus of the Kvbeta1 protein demonstrates that this subunit displays a novel expression pattern in the developing mouse brain. Kvbeta1 expression is high at birth in all brain regions examined and decreases with age. In contrast, Kvbeta2 expression is low at birth and increases with age to reach adult levels by the third postnatal week. These findings support the notion that the differential regulation of distinct potassium channel beta subunits, in the developing mouse nervous system, may confer the functional diversity required to mediate both neuronal survival and maturation.

Aging↗