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Biomedical subjects

D Conti

Publications and source records attributed to D Conti.

36 records · Page 2Linked to original sources
PubMed1990

In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts.

These studies test whether allograft rejection can be blocked by interference with leukocyte adhesion, using a murine IgG2a mAb (R6.5) reactive with monkey ICAM-1 (CD54). In 16 Cynomolgus renal allograft recipients, R6.5 was administered prophylactically as the sole immunosuppressive agent for 12 days (0.01 to 2 mg/kg/day). Survival in 14 recipients with technically successful grafts was significantly prolonged (24.2 +/- 2.4 vs 9.2 +/- 0.6 days for controls; p less than 0.001). Intercellular adhesion molecule-1 (CD54) (ICAM-1) was expressed on vascular endothelium in the kidney and other organs in the monkey in a pattern similar to that in humans. During cellular rejection in controls, ICAM-1 expression increased on endothelial cells, infiltrating mononuclear leukocytes and tubular cells. Biopsies during R6.5 administration showed decreased T cell infiltration (CD2, CD8, CD4) compared with controls and decreased arterial endothelial inflammation. No changes occurred in circulating T cells, aside from variable coating with mIgG. In six of eight other recipients R6.5 administration (0.5 to 2 mg/kg/day for 10 days) reversed preexisting rejection that resulted from taper of Cyclosporine to subtherapeutic levels. Responding grafts showed decreased edema and hemorrhage but no consistent change in the infiltrate. At 1 h after the first dose, mouse IgG deposited primarily on the graft vascular endothelium without any change in the inflammatory infiltrate. Mouse IgG also deposited on the endothelium of normal organs without eliciting an inflammatory response and was cleared from the endothelium within 4 days. Inasmuch as the principal site of binding was the vascular endothelium, we hypothesize that the antibody blocks adhesion to graft ICAM-1 molecules on the vessels. Anti-ICAM-1 also binds to recipient cells and may interfere with Ag presentation and/or T cell interactions. Whatever the mechanism(s), these studies indicate that an anti-ICAM-1 antibody inhibits T cell mediated injury in vivo, and that ICAM-1 is a critical molecule in the pathogenesis of allograft rejection.

Animals↗
PubMed1990

Long-term, low-dose cyclosporine treatment of renal allograft recipients. A randomized trial.

Ninety-two adult renal allograft recipients, receiving baseline immunosuppression with CsA and prednisone, were assigned randomly to one of the following regimens. CsA was discontinued (D/C group) in 47 recipients who were then maintained on Aza and prednisone; or Aza was added to continued low-dose CsA and prednisone (triple drug [TD] group) in 45 patients. Entry into the study required an absence of rejection and a stable creatinine for at least four months prior to randomization. The mean month of randomization was 8.34 +/- 2.9 for the D/C group, and 7.2 +/- 3.2 for the TD group. Following randomization, a significantly greater rate of rejection (P less than .01) was observed in the D/C group (40%) than in the TD group (13%). With a mean follow-up of 30 months, 41/47 of D/C allografts (87.2%) and 39/45 TD allografts (86.6%) were functioning. Nevertheless, rejection had a persistent adverse effect on allograft function, in both the D/C and TD groups, up to 36 months following randomization. Parameters such as donor-type and rejection prior to randomization did not identify recipients at risk for rejection following randomization. Therefore, although the CsA withdrawal regimen might be ideal, the opportunity to select appropriate candidates remained elusive. In contrast, the safety of the TD regimen became apparent. Neither significant nephrotoxicity nor hypertension was observed, and the opportunity for less daily prednisone was evident. Despite its additional cost, the TD regimen utilizing indefinite low-dose CsA, is preferred.

Adult↗
PubMed1990

Xenograft rejection of class I-expressing transgenic skin is CD4-dependent and CD8-independent.

B10.PD1 mice are transgenic animals expressing a class I MHC antigen of pigs. B10.PD1 skin graft survival on B6 mice was prolonged by anti-CD4 antibody treatment in vivo but not by anti-CD8 treatment. These results suggest: (1) that the defect in cell-mediated recognition of xenografts involves an interaction with the xeno-MHC antigens themselves and not with the cells which express them; (2) that antigen processing and presentation of xeno-antigens on responder-type APCs is required in vivo; and (3) that CD8-independent, possibly noncytotoxic, mechanisms of xenograft rejection may exist.

Animals↗
PubMed1990

[Micronuclei induced by ultraviolet radiations or X rays in mammal cells in vitro].

The effects of UV light or X rays in cultured Chinese hamster cells have been initially analyzed in terms of cell growth and colony survival. On the basis of these preliminary observations the induction of micronuclei has been studied on the same in vitro system. The increase in micronuclei yield appears to be dose-dependent, but also to vary according to the protocol used for micronuclei preparation. In general, the results confirm the hypothesis that micronucleus production is a dynamic phenomenon.

Animals↗
PubMed1989

Lymphoproliferative disorders and hematologic malignancies following organ transplantation.

Eleven allograft recipients (one cardiac, one hepatic, nine renal) at the Massachusetts General Hospital developed a lymphoproliferative disorder or leukemia. Six (all renal) patients received conventional immunosuppressive therapy (CIT), four received cyclosporin A (CsA) (one cardiac, one hepatic, two renal), and one received CIT for his first transplant and CsA for his second transplant (both renal). The interval from transplant to onset of the hematologic disorder ranged from 2 mo to 3 yr in the CsA group and from 6 mo to 9 yr in the CIT group and was 16 yr in the patient with two allografts. There were eight malignant lymphomas, seven of which were extranodal, (four immunoblastic, one large noncleaved cell, one small noncleaved cell, one plasmacytoma, one unclassifiable), one case of polymorphic diffuse B cell hyperplasia and two cases of acute myeloid leukemia. Frozen section immunohistochemistry in six cases showed monotypic immunoglobulin in four lymphomas, (including the plasmacytoma), an immunoglobulin-negative B cell phenotype in one lymphoma, and polytypic immunoglobulin in the case of polymorphic hyperplasia. One lymphoma showed a monotypic immunoglobulin-producing B cell population in one site and an immunoglobulin-negative B cell population in another site. With an immunoglobulin heavy chain gene-specific probe, Southern blot analysis of tissue from these two sites revealed two distinct rearrangements. When tissue from a second case of lymphoma was analyzed by Southern blot, identical rearrangements of the heavy chain gene were found in tumor from two separate sites. Similar to the experience of others, we find an increased incidence of lymphoma and a slightly increased incidence of acute myeloid leukemia in allograft recipients. In contrast to other reports, we found a predominance of monoclonal B cell malignancies, a more polymorphous histologic appearance of the lymphoproliferative disorders in CsA patients, and one case each of "multiclonal" and "monoclonal" lymphomas when tumor from separate sites was tested for gene rearrangement.

Adolescent↗
PubMed1976

"Normal-pressure" hydrocephalus. Relationship of clinical and radiographic findings to improvement following shunt surgery.

Analysis of 25 patients who fulfilled clinical and radiographic criteria for the diagnosis of "normal pressure" hydrocephalus (NPH) demonstrated (1) a significant relationship between presence of motor signs with good outcome and absence of motor signs with poor outcome following ventricular shunting, (2) symptoms and signs of parkinsonism in 40% of patients in whom the diagnosis of NPH was made, and (3) no reliable relationship between radiographic measurements or cisternogram appearance and outcome following shunting. The clinical picture is the most important factor in selection of NPH patients for surgery.

Adult↗
PubMed1975

[Clinical and genetic aspects of the early form of Steinert's dystrophia myotonica].

Observations relating to 18 cases of the neonatal form of myotonic dystrophy are described. These consisted of 9 cases of severe forms incompatible with survival, characterised by major respiratory disorders, hypotrophia and difficulty in swallowing, associated with a facial diplegia and pes equinus. The other 9 patients suffered from more moderate, not lethal forms. In addition to muscular troubles manifested by precocious hypotonia, the disease involved serious mental retardation. The absence of myotonia was constant in the very young infants. Anomalies in pregnancies resulting in the birth of children suffering from a neonatal form of myotonic dystrophy are analysed and their frequency is emphasized. From the genetic point of view, the elective transmission of myotonic dystrophy by the mothers was found in all the cases. The knowledge of neonatal forms must be taken into consideration for genetic counseling.

Female↗
PubMedDate not supplied

[The hypoglycemic reactions in diabetic patients in the emergency room. Which patients are going to be hospitalized?].

In one year, a retrospective study in a casualty department identified 67 hypoglycemic episodes occurring to adult diabetic patients: 40 insulin-treated, 20 oral antidiabetic-treated, 7 with unrecorded treatment. All the oral antidiabetic-treated patients were on glibenclamide and the mean dose was 6.5 mg/day: 35.7% of the patients admitted to the medical ward were discharged without antidiabetic drug prescription, suggesting that previous treatment had been unnecessary. Thirty one of the subjects had to be admitted to the medical ward: they were significantly older, mainly on oral antidiabetic treatment and their glucose blood levels were significantly lower than those of the patients treated in the casualty department and sent home. The subjects were admitted mainly because of associated disease, late complications of the diabetic status or home care shortage.

Adult↗
PubMedDate not supplied

Renal effects of low dose aprotinin in pediatric cardiac surgery.

Two groups of 15 children aged from 15 days to 6 years, undergoing surgery on cardiopulmonary by-pass for congenital heart disease have been retrospectively analyzed. Group A received a low-dose aprotinin treatment (30,000 KIU/kg in the priming solution); group C (control group) did not receive any aprotinin. Groups were homogeneous for pathology, cardiopulmonary by-pass time, aortic cross-clamping time, cyanotic/acyanotic patients ratio, temperature during cardiopulmonary bypass. A number of postoperative data were measured: activated clotting time was without any difference between aprotinin-treated and control patients; the same went for temperatures, urine output, intubation time, stay in Intensive Care Unit, coagulation tests, platelet counts, hematocrit, survival rate, and blood loss. Serum creatinine levels were significantly higher in group A than in group C both at the arrival in Intensive Care Unit (0.81 +/- 0.27 vs 0.66 +/- 0.12, p = 0.032) and in the first postoperative day (1.01 +/- 0.5 vs 0.72 +/- 0.19, p = 0.038). BUN was significantly higher in group A vs group C in the first postoperative day (43.6 +/- 21.1 vs 33.9 +/- 16.7, p = 0.043). We conclude that low-dose aprotinin did not reduce postoperative bleeding; we cannot exclude that higher dosages could be more effective, but the evidence of a moderate tubular function impairment suggests caution in using high-dose aprotinin in children.

Aprotinin↗
PubMedDate not supplied

[Cytogenetic dosimetry: dose-effect curves and a methodological comparison].

When physical dosimetry is unavailable, the biological dosimetry of ionizing radiations is considered the best method for evaluating the individual absorbed dose. In order to apply this method, it is essential to know the dose-response relationship (calibration effect) regulating the phenomenon. The results obtained on human lymphocytes after in vitro X-ray treatment are presented. Two cytogenetic methods were used: the dicentric chromosomes assay in metaphase cells and the micronuclei assay in binucleated cells. The two were compared in order to verify the best utilization of each in the context of prevention and radioprotection. For the dicentric assay, 20 samples were treated with increasing doses of X-rays (from 0.5 to 2.0 Gy) and for the micronuclei assay, 25 samples were treated with doses from 0.1 to 4.0 Gy. The biological response was then evaluated. The data obtained were fitted by a second-grade polynomial regression. The dose-response relationship for the dicentric yield was F(dic) = 0.01-0.2D + 0.091D2 (regression coefficient better than 0.95); for the micronuclei yield, it was F(mn) = 0.015 + 0.043D + 0.083D2 (regression coefficient better than 0.97). The absorbed dose in exposed individuals was evaluated by the micronuclei frequency using a mathematical process (inverse prediction) that takes into account the measurement error and the 95% confidence intervals of the calibration curve. For this purpose a programme in Basic (DOSIME) was generated that was capable of estimating the dose and its variability. Since the micronuclei assay is simple and quick to carry out, it permits extensive screening and facilitates the identification of radiosensitive subjects. The estimated dose values of individuals submitted to radiotherapy are also given.

Adult↗