Seroepidemiology of HEV and HAV in two populations with different socio-economic levels and hygienic/sanitary conditions.

The epidemiological scenarios of hepatitis E virus (HEV) and hepatitis A virus (HAV) infections have changed in the last few decades, but precise epidemiological data on the prevalence of anti-HEV and anti-HAV, alone or in combination, in the general population are scanty. We investigated HEV and HAV seroprevalence comparing two population samples living in Northern (Abbiategrasso, Milan) and Southern Italy (Cittanova, Reggio Calabria), the latter being characterized by a poorer socio-economic level and hygienic/sanitary conditions. Based on census records, we randomly enrolled and tested 3,365 subjects (Abbiategrasso, n = 2,489; Cittanova, n = 876) aged 18-75 years for anti-HAV and anti-HEV. Anti-HAV (71.3 % vs 52.5 %) and anti-HEV (17.8 % vs 9.0 %) prevalence rates were higher in Southern Italy (both p < 0.001). Most anti-HEV-positive subjects also had anti-HAV. Subjects testing positive for anti-HAV, alone or with anti-HEV, were older (p < 0.001 in both populations) and showed a trend toward declining prevalence in the youngest birth cohorts. The prevalence of subjects with a positive result for anti-HEV alone did not change in birth cohorts in the two towns. Detection of anti-HEV was independently associated with anti-HAV, town, birth cohort, and education level in multivariate analysis. Low socio-economic level and hygienic/sanitary conditions are associated with high HAV and HEV seroprevalence rates in Italy. Recent improvements, especially in the South, have led to a declining prevalence of anti-HAV, alone or with anti-HEV. Seroprevalence of HEV alone is uniformly low and does not change in birth cohorts born between 1938 and 1993.

Coronary artery disease: evidence of interaction between PTPN22 and p53 genetic polymorphisms.

OBJECTIVES: We recently reported an association between the PTPN22 genetic polymorphism and coronary artery disease (CAD) in nondiabetic subjects. Since recent studies suggest that p53 may be involved in coronary atherosclerosis, we have investigated a possible interaction between PTPN22 and p53 codon 72 genetic polymorphisms regarding their effects on susceptibility to CAD in nondiabetic subjects. METHODS: The genotypes of p53 codon 72 and PTPN22 were determined by DNA analysis in 128 nondiabetic subjects with CAD, 122 healthy blood donors and 117 nondiabetic subjects with cardiovascular diseases without CAD. RESULTS: In subjects with the *Arg/*Arg genotype of p53 codon 72, no association was observed between CAD and PTPN22. However, this association was very strong in subjects carrying the *Pro allele of p53 codon 72. Subjects carrying both the *T allele of PTPN22 and the *Pro allele of p53 were overrepresented in CAD nondiabetic cases relative to the other two groups (p = 0.001). CONCLUSIONS: Since both p53 and PTPN22 are involved in autoimmune inflammation, an interaction between the two systems appears biologically plausible. In the analysis of multifactorial disorders, the simultaneous analysis of multiple genes functionally related to diseases will provide a more productive approach than studies of single genetic factors performed from a Mendelian perspective.

Management of highly sensitized patients: capitol medical center experience.

Highly sensitized patients with elevated anti-HLA antibodies have difficulty to get a living donor due to cross-match positivity and longer waiting times for cadaveric donor transplantation. In this regard, several studies have been made to abrogate cross-match positivity for a possible successful kidney transplantation. In this article, we report our experience, using a desensitization protocol with Rituximab monoclonal antibody complemented with intravenous immunoglubulin and/or plasmapheresis, to prepare highly sensitized patients for successful kidney transplantation.

The correlation of renal allograft weight to metabolic index ratios and glomerular filtration rate among living-unrelated kidney transplant patients: a cross-sectional study.

OBJECTIVE: This study sought to determine whether there was a relationship between the ratios of renal allograft weight (RAW) and metabolic indices: specifically, recipient body weight (RBW), recipient body mass index (RBMI), and recipient body surface area (RBSA), and posttransplant renal function as measured by glomerular filtration rate (GFR). It also sought to determine which of the 3 ratios, and the minimum ratio, that was predictive of a good GFR as well as to ascertain which computational formula (Cockroft-Gault [C&G] vs abbreviated Modification of Diet in Renal Disease [aMDRD]) better predicts renal function. METHODS: This cross-sectional study was performed among living unrelated kidney transplant patients who did not manifest rejection, ischemic injury, or postoperative morbidity and mortality from January to December 2006. Donor/recipient matching was based on conventional immunologic parameters. The harvested kidney was weighed after a cold bath and then transplanted by a single surgical team. The 3 ratios, RAW/RBW, RAW/RBMI, and RAW/RBMI were correlated with GFR, which was computed using C&G and aMDRD formulae based on serum creatinine at discharge and at 6 months follow-up. Statistical analysis used STATA 7 and the Pearson correlation using linear regression analysis. RESULTS: The 53 kidney transplant patients has a mean age of 39.8 years +/- 19 SD (range, 6-74), and slight male predominance (58% vs 42%). RAW/RBW was most positively correlated with GFR estimated by aMDRD (r = .89; P < .001) but negatively correlated with GFR estimated by the C&G formula both at discharge and at 6 months follow-up. A similar trend was observed with RAW/RBMI (r = .79; P < .001), whereas RAW/BSA was related to neither GFR formula. Of the 3 ratios, RAW/RBW best predicted GFR using the aMDRD formula. The minimum RAW/RBW ratio that predicted good GFR (>90 mL/min) at 6 month follow-up was 8.2 (accuracy 88.6%; P = .004). CONCLUSION: The RAW/RBW and RAW/RBMI correlated with GFR measures by the aMDRD method. Of the 3 ratios, only RAW/RBW was useful to predict GFR, best estimated by the aMDRD formula. A minimum RAW/RBW ratio of 8.2 predicted a good GFR at 6 months posttransplant. The findings suggested that transplanting a small kidney into a heavy patient may be a risk factor for allograft failure and that having a high initial ratio (> or =8.2) of renal allograft weight to initial recipient body weight was an advantage.

Functional aspects of genetic variability in the GH genomic region.

Because of the small differences among genotypes, it would be difficult in basal conditions to detect the effect of genetic polymorphism in endocrine function, but this could emerge during provocative tests. We have studied four polymorphic sites of the GH gene region (17q24.2), MSPIA, MSPIB, BGLIIA, and BGLIIB. Gene and haplotype distributions in classes of growth retardation have been studied. The outcome of GH diagnostic test in relation to GH region genotypes has been evaluated by the analysis of area under the GH secretory curve. Ninety-eight growth retarded children have been studied. On the basis of provocative GH test these children were classified as total GH deficit (TD), partial GH deficit (PD), and familial short stature (FSS) with no deficit of GH. Sixty-three healthy controls were also considered. An increased frequency of MSPIA*2 allele in PD and TD as compared with FSS children and controls has been observed suggesting that this allele is associated with a decreased GH release. BGLIIA*2 allele appears decreased in PD and TD as compared with FSS and controls, suggesting that this allele is associated with an increased release of GH. Carriers of MSPIA*2 allele show a lower GH release as compared with MSPIA *1/*1 subjects on the provocative test by insulin, while carriers of BGLIIA*2 allele show a higher GH release as compared with BGLIIA *1/*1 subjects on the provocative test by clonidine. The functional aspects of genetic variability within the GH genomic area parallel the genetic differences observed between TD and PD versus FSS and control children.

Relationships between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis.

The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis.

The genetics of signal transduction and the outcome of diagnostic tests in growth retardation.

The effects of 'normal' genetic variability of signal transduction on endocrine function may be more evident during stimulation tests than is observed in basal states, thereby contributing to a greater understanding of the possible role of signal transduction genetics in the pathogenesis of endocrine disorders. In the present study, we have studied the outcome of growth hormone (GH) stimulation testing by insulin in growth-retarded children in relation to the genotype of ACP1 (acid phosphatase locus 1; also referred to as cLMWPTP, cytosolic low molecular weight phosphotyrosine phosphatase). ACP1 is an enzyme, expressed as two distinct isoforms designated F and S, that down-regulates insulin receptor signal transduction and which shows a genetic polymorphism with strong quantitative enzymatic differences among genotypes. In this study, we examined 116 growth-retarded children of which 101 were genotyped for ACP1. We found that the basal level of GH is higher in ACP1 genotypes with low concentrations of the S isoform than in genotypes with high S isoform concentrations (P<0.02). Additionally, during GH stimulation with insulin, the genotypes with low S isoform concentrations were found to perform better (P<0.005) and to react more promptly than the genotypes with high S isoform concentrations (P<0.05). These findings suggest that high S isoform ACP1 activity slows down the effect of insulin, resulting in a retardation of its metabolic effect.

Rh system and intrauterine growth. Interaction with season of birth.

Based on the hypothesis that maternal-fetal genetic differences in membrane transport and signal transduction may influence intrauterine development, the recent acquisition on transport function of Rh protein prompted us to study the relationship between joint maternal-fetal Rh phenotype and birth weight. Considering that metabolic effect of maternal-fetal competition could be amplified by environmental conditions, we have investigated possible seasonal effects on such relationship. We have studied 5291 infants born in Sardinia in the period January 1993--December 1996 and 984 infants born in Rome during 1996. In Rh(-) mothers there is a significant association between season of birth and birth weight that shows the highest mean value in infants born in autumn (i.e. conceived in winter). The association is much more evident in male than in female infants. In male infants from Rh(-) mothers, the association between birth weight and season is significant in Rh(+) male newborns only. Recent observations by our group in NIDDM suggest that glucose transport in RBC may be related to D protein, thus we propose an interpretation of the present observation in terms of transport function. When the density of D protein in the infant is greater than in the mother, the balance is in favour of the infant who may attain a significant developmental advantage when conceived in the cold season.

Further studies on acid phosphatase in obese subjects.

Low activity genetic variants of acid phosphatase (ACP1) are positively associated with extreme body mass deviations in obese subjects. The same pattern has been found in non-diabetic children, in diabetic pregnant women, and in non-diabetic adult subjects. Low activity variants of ACP1 also show a positive association with family history of obesity, supporting the hypothesis of an enhancing action of these variants on expressivity of obesity.

Phosphotyrosine-protein-phosphatases and human reproduction: an association between low molecular weight acid phosphatase (ACP1) and spontaneous abortion.

ACP1 (low molecular weight acid phosphatase) genetic polymorphism has been studied in 173 women with a history of two or more consecutive spontaneous abortions and in 1508 control subjects, including 482 normal pregnant women. The proportion of carriers of ACP1*C allele (*A/ *C, *B/*C) in women with a history of repeated spontaneous abortion is lower than in normal pregnant women and other control groups. Women with repeated spontaneous abortion show a specific decrease of ACP1 S isoform concentration as compared to normal pregnant women. The other component of ACP1 activity, the F isoform, does not show a significant difference between the two groups. The data suggest that women with ACP1 genotypes showing a high concentration of S isoform are relatively 'protected' against spontaneous abortion. Preliminary analysis of a sample of 352 normal puerperae along with their newborn babies supports this hypothesis.

Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation.

We studied 101 growth-retarded children from the population of Ancona (Italy). Plasma growth hormone (GH) levels at the end of insulin and clonidine tests were considered for classification of children into 3 categories according to severity of GH deficit: total deficit of GH (TD), partial deficit (PD, and familiar short stature (FSS; no deficit of GH). The BGLIIA*2/BGLIIB*1 haplotype of GH cluster that was previously found to be negatively associated with severe glucose intolerance in non-insulin-dependent diabetes mellitus (NIDDM) is negatively associated with GH deficit in growth-retarded children. The hypothesis that intrauterine growth retardation and glucose intolerance in adult life could be phenotypes of the same underlying genotype has been recently put forward. The present observation suggests that genes influencing both growth and glucose tolerance are encoded in the GH cluster.

Technical complications of renal transplantation.

This article reviews the technical complications of renal transplantation that may manifest early or later during the post-transplant period. Complications arising from the preparation of the transplant bed to the establishment of urinary tract continuity are discussed. An aggressive approach to readily diagnose and expeditiously treat such complications offers a better result with fewer graft losses and reduced morbidity.

Foetal macrosomia and erythrocyte acid phosphatase (ACP1) polymorphism in diabetic and normal pregnancy.

Both in diabetic and in normal pregnancy the proportion of macrosomic fetuses is much lower among newborns carrying Pc allele of erythrocyte acid phosphatase (ACP1) than among other ACP1 genotypes. In diabetic pregnancy the well known increased incidence of fetal macrosomia has been observed only among fetuses which do not carry this allele. ACP1 probably functions as a flavin-mononucleotide phosphatase. Since Pc allele is associated with the highest enzymatic activity it is likely that subjects carrying this gene may have a relatively lower concentration of flavin-mononucleotide cofactors and in turn a reduced rate of metabolic activities controlled by flavoenzymes. It is possible that in fetuses carrying Pc, flavo-enzyme activities are regulated at a level that does not allow a full response to stimuli (both genetic and/or environmental) aimed to maximize fetal growth.

Oral cyclosporine preparations immediately following renal transplantation.

A cohort of 11 patients receiving de novo CyA-GC was compared to 11 patients receiving CyA-ME immediately following renal transplantation at five-dose intervals in the first 30 postoperative days. Neither group achieved target CyA concentrations during days 0 to 2, suggesting that additional immunosuppression exposure coverage may be needed at that interval. Thereafter, however, recipients of the CyA microemulsion (Neoral) formulation reached target levels earlier as well as required lower doses to reach target levels.

Intrauterine development and MNSs blood groups in repeated spontaneous abortion.

OBJECTIVES: To determine whether the maternal MNSs genotype has an effect on the birth weight and gestation duration of the live offspring of women with repeated primary spontaneous abortion (RSA). METHODS: The study sample consisted of 239 healthy white women who had been delivered of a live infant, and 137 women with a history of primary RSA-54 of whom had recently been delivered of a live infant and 83 who had had a spontaneous abortion. Maternal MNSs phenotypes were determined by standard serological methods, and the results were analyzed for relationships between these phenotypes and the mothers' reproductive status and the infants' birth weight and gestational age. Analysis of variance, the chi(2)-test of independence, and the Mantel-Haenszel test for linear association were performed for data analysis. RESULTS: Infants born to mothers with the Ss genotype showed significantly lower birth weight and gestational duration compared with the infants of mothers with other genotypes. Additionally, the MNSs haplotype was found to be associated with birth weight. CONCLUSIONS: Previous studies have shown that the MNSs system influences the gestational age of aborted fetuses in cases of RSA. The present study supports the hypothesis that this genetic factor influences intrauterine growth and development in women experiencing RSA.

ABH secretor genetic polymorphism: evidence of intrauterine selection.

OBJECTIVE: Fucosyltransferase locus 2 (FUT2) controls the presence or absence of blood group substances (A, B, H) in the saliva and other body secretions. Secretor/non-secretor phenotypes are associated with some metabolic and infectious diseases. ABO and FUT2 contribute to build up oligosaccharide structures of the cell surface that are important for blastocyst adhesion and resistance to microbial invasion. We investigated a possible selection on ABH secretor phenotypes during intrauterine life. STUDY DESIGN: Three hundred and fifty-six consecutive healthy puerperae and their newborn infants from the caucasian population of Rome were studied. Informed consent for study participation was obtained from the mothers to participate and the study was approved by the Institutional Review Board. ABH secretor Se phenotype was determined on saliva by standard laboratory procedure. RESULTS: Symmetry analysis of mother infant Se phenotype revealed a deficit of mother Se+/newborn Se- with respect to expected values. The asymmetry is present only in infants carrying the A blood group antigen. The asymmetry was dependent on several maternal and neonatal parameters including maternal age, smoke, parity and gestational duration. CONCLUSIONS: The data suggest intrauterine selection against Se- of the embryo carried by a Se+ mother. Such selection is dependent on factors influencing the maternal environment. The study could have practical importance in assessing the risk of infertility and success of artificial insemination.

Haptoglobin phenotype and reproductive success in repeated spontaneous abortion.

OBJECTIVE: To study the reproductive success of couples with a history of repeated spontaneous abortion (RSA) with respect to the haptoglobin (Hp) phenotypes of both the wife and husband. STUDY DESIGN: This study examined maternal and paternal Hp in 194 couples with primary and secondary RSA recruited from the Center for Reproductive Disorders of the Institute of Obstetrics and Gynaecology at the University of Rome, La Sapienza. Reproductive success was indicated by the presence of at least one live-born infant after more than 5 years of follow-up. RESULTS: The proportion of wives carrying Hp2/1 phenotype and with at least one live-born infant is significantly lower than that of wives without a live-born infant. Moreover, the proportion of couples in which both wife and husband possess the Hp2/1 phenotype is much lower in those with at least a live-born infant than in those without a live-born infant. Both maternal and paternal Hp contribute to reproductive success. However, the contribution of maternal Hp appears stronger than that of paternal Hp. CONCLUSIONS: Hp may play an important role in implantation and/or embryo survival. Couples in which both partners carry the Hp2/1 phenotype have a low probability of producing a live-born infant.

Antiviral treatment for hepatitis C virus infection: effectiveness at general population level in a highly endemic area.

BACKGROUND: Peginterferon plus ribavirin treatment induced a sustained virological response in >50% of HCV-RNA-positive individuals enrolled in published clinical trials. AIM: To determine anti-HCV treatment effectiveness at a general population level. PATIENTS AND METHODS: In 2002, a 1:5 random sample of >11 years old inhabitants of a small Italian town (Cittanova) was invited for HCV screening. HCV-RNA-positive individuals were evaluated for antiviral treatment. RESULTS: 1645 of 1924 invited individuals (85.5%) participated in the screening. 84 HCV-RNA-positive individuals were detected: median age was 65 years (range: 32-87); 67% was infected with genotype 1 or 4. Antiviral treatment was judged unnecessary for 43 (51.2%), due to persistently normal alanine aminotransferases, mild disease at liver biopsy or age >70 years without cirrhosis. Twenty-eight of the remaining 41 patients (68.3%) were ineligible for treatment, because of medical/psychiatric contraindications (42.9%), alcohol/drug abuse (17.9%), decompensated cirrhosis/hepatocellular carcinoma (17.9%), not attending official appointments (10.7%), previous intolerance/non-response to interferon plus ribavirin (10.7%). 5 of 13 eligible patients (38.5%) did not receive treatment (4 refused and 1 accidental death). 3 of 8 treated patients (37.5%) reached a sustained virological response. CONCLUSIONS: Although efficacy of anti-HCV therapy improved in recent years, we found that low eligibility to treatment still limited its effectiveness at general population level in a highly endemic town.