Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an italian population.

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the progression of immunoglobulin A glomerulonephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of IgA-GN was studied. A logistic regression model showed that the risk for homozygous DD was not significantly elevated in patients with IgA-GN compared with healthy subjects (odds ratio = 1.16; confidence interval [CI], 0.4 to 3.3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; chi2 = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox proportional model after adjustment for known factors of progression, such as hypertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR for heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with progression was even more striking when patients with other risk factors (heavy proteinuria) were excluded, as shown by DD-related risk in the absence (HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The risk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients with IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the end-stage renal failure subgroup compared with the normal renal function subgroup (odds ratio = 3.16; CI, 0.7 to 13.7) after adjustment by sex, age at biopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in those patients who started hemodialysis at an earlier age (chi2 for trend = 6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical course. However, on the basis of current knowledge, we cannot exclude that I/D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage.

Cytotoxic T lymphocyte precursor frequency as a predictor of acute graft-versus-host disease in bone marrow transplantation from HLA-identical siblings.

The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the severity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marrow transplantation (BMT). In HLA-identical sibling BMT, where aGVHD is most likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive information. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA identity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB was tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses. Fifteen out of 21 (71%) patients with high precursor frequency (>1:100 x 10(3)) and 12 out of 30 (40%) with low precursor frequency (<1:100 x 10(3)) experienced clinically significant (II-IV) aGVHD. A significant correlation (P = 0.04) between CTL-p frequency and severe aGVHD was demonstrated. Moreover there was a positive trend for a high frequency response according to an increasing grade of aGVHD, which was statistically significant (P = 0.04). In our experience the CTL-p assay is a helpful predictive test for aGVHD in HLA-identical sibling BMT, indicating high risk patients possibly requiring additional prophylaxis.

HLA antigens and clinical manifestations in Crohn's disease.

A clinical, radiological and immunogenetical study was carried out on 51 Crohn's patients. Rheumatological disorders were found in 16 of them, with higher frequency in those with colon involvement only. A statistically significant increase in the frequencies of HLA-A9 and HLA-Cw3 was noted: Cw3 showed a particularly high frequency in males, and A9 in younger patients. The frequency of HLA-B27 was significantly increased in the patients with colon involvement. In the group of 16 patients with rheumatic diseases HLA antigen frequencies were not significantly different from the control population.

Waiting list for kidney transplant. Some patients wait too long.

The selection of a kidney graft recipient should be made not only taking into account biological and clinical parameters, for assuring the maximum possible clinical success; the ethical objective to allow every patient equal opportunity of receiving a transplant should also be pursued. In every waiting list of transplant candidates a proportion of patients remains in the list for a particularly long time. The present analysis aimed to find out the factors associated with a prolonged waiting time, in order to allow the implementation of patient selection criteria able to balance unfavourable factors. The analysis of the waiting list of our kidney transplant centre allowed to observe that blood group 0, anti-HLA immunisation, presence of rare HLA antigens and, at a lesser extent, HLA homozygosity are associated with a longer waiting time for a kidney transplant.

[Pregnancy after kidney transplantation. Review of the international literature and presentation of personal case reports]. / Gravidanza dopo trapianto di rene. Revisione della letteratura internazionale e presentazione della casistica personale.

BACKGROUND: Advances in surgical techniques and immunosuppression have improved the results in organ transplantation. The quality of life in these patients is good in the most of cases and pregnancy, which means for them to resume a normal life, isn't an exceptional event, specially for kidney transplant recipients. METHODS: Retrospective data regarding pregnancies observed at the Dept. of Nephrology and Dialysis of the S. Giovanni Battista Hospital in Turin, have been collected to value the pregnancy frequency and outcome (complications, miscarriage, therapeutic abortion), the mother follow-up as a function of transplant rejection risk, the newborn conditions, their hematological and immunological situation, and the children follow-up. RESULTS: This study includes 9 pregnancy (6 at term and 3 abortions), observed since 1987 in 6 kidney transplant recipients. Congenital malformations or immunological diseases have not been observed; according to the literature, there was a high frequency of preterm delivery and intrauterine grow retardation. Complications during pregnancy were observed in 5 cases (83.3%). CONCLUSIONS: The study confirms that kidney transplant recipients can carry a pregnancy through and give birth to healthy infants, but these pregnancies are to be regarded as being at high risk and require a multi-disciplinary approach.

[Study of a group of families with high incidence of schizophrenia]. / Studio di un gruppo di famiglie ad alta incidenza di schizofrenia

The pedigrees of six schizophrenics' families presenting a very high percentage of sick subjects, (near to 50%) are studied. The data obtained allow to think to an hereditary transmission of the mental disease, in these families, as an autosomal dominant character; the responsible gene may have a reduced penetrance and a variable expressivity. The comparison of these data with those obtained from other schizophrenics' families support the hypotesis of an unomogeneus genetic basis for schizophrenia and also the supposition that a severe mutation of the principal gene has occurred in the studied families.

[Transplantation collaborative networks]. / Le reti collaborative per i trapianti.

The collaborative networks in Italy are described, with their objectives and the geographical areas covered. Their main features are: function of the reference centres, waiting lists, criteria for organ assignment, common programmes for some patients, services offered to the network members, organ procurement activity. The analysis of the activities performed included organ exchanges within and outside the network, common activities for tasks that could not be satisfactorily attained by a single centre or region, the collaborative studies. Finally, the role of the networks and of a national coordination, in order to better develop transplants nationwide, is discussed.

[Waiting lists for transplantation in Italy]. / Le liste di attesa trapianto in Italia.

To plan health services it is essential to gauge the needs. In transplant field in Italy, the first suitable data for waiting lists were collected in 1998. The data collected by Istituto Superiore di Sanità gave us a shot of patients field in waiting list at that time. We here analyse more significant data about heart, liver and kidney waiting lists. The situation is very different among north, centre and south of Italy: in South, where transplant activity is low, we found rare transplant centres, and most of patients prefer north centres. In kidney waiting list we found 1100 patients living in southern regions but registered in the waiting list of a different region. These data can help in planning development lines in Italy.

[Genetic analysis of Italian hematologic patients candidates for bone marrow transplantation from unrelated donors]. / Analisi genetica di pazienti ematologici italiani candidati al trapianto di midollo osseo da donatore non consanguineo.

Frequencies of HLA-A, -B and -DR antigens and haplotypes were determined in 1945 Italian patients suffering from hematologic diseases and requiring bone marrow transplantation from unrelated donors. These frequencies were compared with those obtained from the Italian bone marrow donor population. No significant differences were found when considering the number of comparisons made, suggesting that the genetic structure of the Italian patients is not different from that of the Italian donor population.

[The Italian Registry of Bone Marrow Donors: genetic structure and recruitment strategy]. / Il Registro Italiano dei Donatori di Midollo Osseo: struttura genetica e strategie di reclutamento.

The genetic structure of the Italian bone marrow donor population was analysed by estimating the HLA-A, -B and -DR gene and haplotype frequencies for the total population and for the Italian administrative regions. The haplotype frequencies were used to predict the probability of finding HLA-compatible donors for Italian patients depending on the registry size, and the probability of recruiting in the different Italian regions a donor with a new phenotype. The analysis of these probabilities allows us to propose strategies for donors recruitment in order to increase the phenotypic variability of the registry, then its efficiency.