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R Carrano

Publications and source records attributed to R Carrano.

10 recordsLinked to original sources

Opinions on renal transplantation and organ donation in high school students in two large northern (Torino) and southern (Napoli) Italian cities.

UNLABELLED: Organ shortage for transplantation has focused attention on educational interventions. Italy is a nonhomogenous country whose cultural and economic differences are reflected in the health-care system: dialysis is mainly public in the north versus private in the south; and transplantation rates display a wide range from 3.4 to 37.8 per million people in 2002. The aim of the present study was to analyze the opinions of population of high school students (last two years) in two large cities: northern (Torino) and southern (Napoli) Italy, as a knowledge base for a randomized controlled trial on the efficacy of educational interventions on renal replacement therapy and organ donation, targeted to high school students. METHODS: This preliminary study included eight public high schools that completed a first and anonymous semistructured questionnaire. Five hundred and eighty nine questionnaires were retrieved in Torino and 539 in Napoli. In both cities most students answered that they would give a kidney to a brother, sister, or partner needing dialysis (Torino: yes 80.6%; no 2.2%, uncertain-blank 17.2%; Napoli: yes 86.1%, no 1.1%; uncertain-blank 12.8%). Only 36.3% of the students in Torino and 37.7% in Napoli answered that they would consent to organ donation, if they had to choose for a strict relative with brain death. Opposition was 28% in Torino and 23.7% in Napoli; 35.7% in Torino and 38.6% in Napoli were blank-uncertain. These data underline the need for detailed information on the opinions of the overall population as basis for tailored educational campaigns.

Adolescent↗

Safety and immunogenicity of HIV-1 DNA constructs in chimpanzees.

A global effort to control the HIV epidemic is likely to rely heavily on immunization strategies. As our closest genetic relative, the chimpanzee provides the most important model for preclinical safety and immunogenicity studies. We have immunized adult, pregnant and infant chimpanzees with our plasmid vaccines. We have found these vaccines to be safe and well tolerated in all of these groups. The same vaccines have induced both humoral and cellular immunity in each instance.

AIDS Vaccines↗

DNA vaccination as anti-human immunodeficiency virus immunotherapy in infected chimpanzees.

The role of the immune response in controlling human immunodeficiency virus type 1 (HIV-1) replication is controversial. Immunotherapeutic strategies that have the ability to broaden immune responses might play a role in slowing disease progression. DNA immunization was studied as immunotherapy in infected chimpanzees. Two HIV-1-infected chimpanzees were vaccinated with DNA plasmid vaccines, one with plasmid pCMN160, which expresses the envelope glycoprotein of HIV-1MN and rev, and the other with a control plasmid. The chimpanzee immunized with pCMN160 demonstrated enhanced humoral responses. Virus load was monitored. Virus load in the chimpanzee receiving pCMN160 decreased at week 20 and has remained at background levels. The control chimpanzee was subsequently vaccinated with pCMN160. After immunization, the antibody responses increased and, as in the first animal, the virus load decreased. These results indicate the potential of the immune response to have a direct impact on HIV-1 replication in chimpanzees.

Amino Acid Sequence↗

DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates.

DNA, or genetic, inoculation mimics aspects of attenuated vaccines in that synthesis of specific foreign proteins is accomplished in the host. These proteins can be processed and presented on the relevant major histocompatibility complex (MHC) antigens and ultimately become the subject of immune surveillance. Very recently, we have described the use of the new technology to generate immune responses in mice against the human immunodeficiency virus type 1 (HIV-1) envelope using a gp160 DNA construct. Further analysis of this technology specifically in regard to HIV vaccine design is clearly important. In this report, we describe the analysis of additional HIV constructs as immunogens in both mice and report the use of this genetic immunization technology in nonhuman primates. In these studies, successful seroconversion occurs in more than 70% of the mice following the second immunization with 100 micrograms of construct DNA; three and four immunizations result in routinely 100% seroconversion of the mice. Furthermore, the same strategy has successfully seroconverted primates following their second inoculation, resulting in the generation of both antiviral and neutralizing antibodies in this animal species. These studies are the first report of which we are aware that demonstrate successful immunization of nonhuman primates through genetic vaccination technology and the first to describe genetic immunization of primates against HIV antigens. This technology has relevance for the development of safe and efficacious immunization strategies against HIV because it provides for relevant antigen production in vivo without the use of infectious agents.

AIDS Vaccines↗

Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. I. Clinical aspects.

Twenty-five patients with metastatic gastrointestinal adenocarcinoma received one to four infusions (400 mg) of murine monoclonal antibody CO17-1A. Eleven patients had mild gastrointestinal symptoms, and one had a transient flushing episode. Two of five who received three weekly infusions had readily reversible anaphylactic reactions at the time of the third infusion (day 15). There were no other toxic effects. One patient had a complete remission and is surviving at greater than 104 weeks, and four had stable disease. The median survival for the whole group was 57 weeks. In general, the antibody infusions were well tolerated but had modest antitumor effects.

Adenocarcinoma↗

Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response.

Twenty-five patients with metastatic gastrointestinal adenocarcinoma received one to four infusions of large doses (400 mg) of murine monoclonal antibody CO17-1A (17-1A). The pharmacokinetics of 17-1A at the time of first, second, third, or fourth infusion were not statistically different; plasma half-lives were 15.0 +/- 1.7 hours (n = 5), 15.1 +/- 1.8 (n = 10), 25.3 +/- 6.2 (n = 3), and 14.4 +/- 1.8 (n = 5), respectively. Most patients had an antibody response to 17-1A, with peak levels occurring 15-22 days after infusion. The presence of serum antibody to 17-1A at the time of the second or third infusion did not significantly alter the pharmacokinetics of this large dose of antibody. Four of 25 patients failed to develop an antibody response, but this did not correlate with the amount of 17-1A administered. The administration of four doses of 400 mg over 1 week provided continuously circulating 17-1A for 10 days.

Animals↗

Phase I clinical trial of CO17-1A monoclonal antibody.

Twenty patients with metastatic gastrointestinal cancer received one or more weekly infusions of 400 mg CO17-1A monoclonal antibody. The most common side effect was mild gastrointestinal symptoms in 9/20 patients. Two of five patients receiving three weekly infusions had reversible anaphylactic reactions at the time of their third infusion. The pharmacokinetics of the antibody were similar at the first, second or third infusion. Human antibody to 17-1A occurred in 17/20 patients with 11/20 having antibody detectable by 8 days following initial infusion. Thus, one or two infusions (weekly) of large doses of 17-1A were well tolerated but allergic responses limit ability to administer therapy by 15 days post-initial infusion.

Animals↗

Comparison of the relative mutagenic activity for eight antineoplastic drugs in the Ames Salmonella/microsome and TK+/- mouse lymphoma assays.

Eight antineoplastic drugs were evaluated for their ability to induce mutation in the Ames Salmonella/microsome and the TK+/- mouse lymphoma assay. Dose response data were utilized to determine the relative potency of each of these drugs. They were then ranked based on this information. Vincristine, the most potent compound tested in the mouse lymphoma assay, was not active in the Salmonella assay, nor were DTIC and Methotrexate. Excluding these compounds from the comparison ranking, we found that the only difference in the order between the Ames and lymphoma assays was between Daunomycin and Adriamycin. Daunomycin was most potent in the Ames assay, compounds was reversed in the mouse lymphoma assay. This observation of relative activity is of interest because it underscores the ability to extrapolate between microbial and mammalian test systems, provided one keeps in mind the differences associated with chromosome structure and modes of segregation in these two cell types. Furthermore, it is suggested that relative potency ranking may provide prospective insight into expectations of risk for human populations exposed to these drugs.

Animals↗

Thyroid function and morphology after a successful kidney transplantation.

Although thyroid disorders related to the end-stage renal disease (ESRD) are well known, there are discordant data on the function and morphology of the thyroid gland after renal transplantation (RT). The objective of this cross-sectional, case-control study was to investigate the prevalence and risk factors for disorders in the thyroid function and morphology after a successful RT. Fifty consecutive patients (25 females, 25 males) with fully functioning allograft were enrolled. Their age at transplant ranged from 23 to 44 yr (median, 38) and their post-RT follow-up lasted 15-86 months (median, 23). One hundred healthy subjects matched for sex, age and body mass index (BMI) were included as controls. Serum free thyroid hormones, TSH, thyroglobulin, thyroid hormone-binding globulin (TBG) and iodine urinary excretion were determined; ultrasonographic exam of the thyroid gland was performed in all subjects. Age, gender, time elapsed from RT, dialysis duration, kidney function, type of immunosuppression and corticosteroid dose were considered as possible influencing factors for the thyroid function. Hypothyroidism was found in 6% of patients, "low T3 syndrome" in 52%, while another 26% had free T3 (FT3), free T4 (FT4) and TSH in the lowest third of the normal range, suggesting inhibition of the whole hypothalamic-pituitary-thyroid (HPT) axis. Iodine excretion and prevalence of anti-thyroid antibodies were similar in both patients and controls. There was no significant difference in the thyroid function according to different immunosuppressive regimens. In patients, an ultrasonographic exam revealed a very variable thyroid volume ranging from 7.2 to 24.8 ml. Solid nodules were detected in 12 (24%) cases and cystic lesions in another four (8%); they were proven negative at cytological examination. Dialysis duration was longer in patients with thyroid nodules than in those without (p<0.05). Inhomogeneous hypoechoic pattern typical for chronic thyroiditis was more frequent than its biochemical expression. In conclusion, a high prevalence of abnormal thyroid morphology was found in patients after a successful RT, being partly related to a previous uremia. Abnormalities in the thyroid function are likely an expression of the post-transplant general and immunological conditions. Endocrinological follow-up is advisable in patients after RT, in order to discriminate thyroid dysfunctions which need specific treatments from those that can only be followed-up, avoiding inappropriate treatments of biochemical abnormalities.

Adult↗