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Biomedical subjects

C De Rosa

Publications and source records attributed to C De Rosa.

At least 19 recordsLinked to original sources
PubMed2006

Combination of all-trans-retinoic acid and gemtuzumab ozogamicin in an elderly patient with acute promyelocytic leukemia and severe cardiac failure.

All-trans-retinoic acid (ATRA) combined with anthracyclines is currently the standard treatment for acute promyelocytic leukemia (APL). In elderly patients the presence of comorbidities, such as cardiomyopathy or different organ failures, often represents an absolute contraindication to standard chemotherapy. In this particular setting of patients, alternative front-line approaches are needed. Here we report the use of gemtuzumab ozogamicin as consolidation therapy in a 68-year-old patient not eligible for standard dose anthracycline due to severe cardiac failure and chronic anticoagulant therapy, affected by low-risk APL. Induction therapy was started with ATRA alone, at a dose of 45 mg/m2 for 80 days. The patient obtained a complete hematological and molecular remission. At day +170 the patient was treated with 6 mg/m2 gemtuzumab ozogamicin monthly for two months (2 total doses) as a consolidation therapy and then started a maintenance program with ATRA 45 mg/m2 for 15 days every three months, for a total time of two years. No adverse events were observed in every phase of treatment and the patient is still in complete continuous hematological and molecular remission 29 months from diagnosis. This approach represents an intriguing therapeutic option to be investigated in randomized studies in low- and intermediate-risk elderly patients (older than 65 years), aiming to minimize or to eliminate standard chemotherapy in advantage of new non-conventional agents, including ATO.

Aged↗
PubMed2004

Development of a model based on body composition to predict drug kinetics-1 evaluation in healthy volunteers.

A kinetic model for widely used drugs, based on body composition analysis, was developed and evaluated in young and elderly healthy individuals. Body composition was studied by body impedance analysis (BIA). Antipyrine, amlodipine, digoxin and tobramycin kinetics, liver microsomal activity enzyme (lidocaine/MEGX test), and appropriate clinical and laboratory tests were carried out. Major variables (V(d), AUC, t(1/2), C(max), Cl) for these drugs were calculated, and the possible relationships with the other clinical and biochemical data were analyzed by the Pearson's moment correlation, forecasting models being then obtained by a multiple linear regression method. Major kinetic parameters, particularly for the mixed elimination drugs (liver/renal), i.e. digoxin and amlodipine, proved to be well correlated to data collected during the study, in particular with body structure parameters. Results were less satisfactory in the case of the mainly renally handled tobramycin. Mathematical models to forecast the kinetic behaviors of the three chosen drugs, using readily accessible data, showed both in the young and the elder, as well as in the whole examined population, very satisfactory correlations in the case of digoxin (R(2) ranging from 0.89 to 0.85) and amlodipine (R(2) between 0.81 and 0.91), less satisfactory (with a wide range of R(2), from 0.65 to 0.94), in the case of tobramycin.

Adult↗
PubMed2004

Development of a model based on body composition to predict drug kinetics; II. Application of the model to the use of digoxin in elderlies.

The applicability of a kinetic model for the prediction of steady-state blood levels, based on body composition as assessed by bioelectric impedance analysis (BIA), was applied to a population of elderly patients, candidates for digoxin therapy. Elderlies, all >70 years of age, underwent standard laboratory and clinical evaluation but no further characterization of liver or renal function. These 72 patients were given 0.125 mg digoxin for 5 days, in order to reach steady-state levels. Treatment was then interrupted and samples were collected 2 and 48 h after the last administration. Plasma digoxin levels were determined both by the immunochemical method with TDX and according to the BIA method described in the accompanying paper. Plasma levels calculated and measured in 2 h samples did not differ statistically, but levels were about 15% higher in the directly measured samples. There was a similar underestimation, i.e. about 15%, for the 48 h calculated levels. However, only approximately 5% of the levels were outside of the 95% confidence intervals as determined from the directly measured levels. These findings indicate that digoxin levels, calculated based on a BIA evaluation, may be sufficiently reliable, in the majority of patients, to allow direct determination of the more appropriate doses of digoxin.

Aged↗
PubMed2001

Identification of Hb Villejuif [beta123(H1)Thr-->Ile] in Southern Italy.

Hb Villejuif [beta123(H1)Thr-->Ile] is a silent and asymptomatic variant described in 1989 in an 87-year-old woman of French origin suffering from coincidental polycythemia vera. This paper reports the second observation of Hb Villejuif in three related subjects from Montesarchio, Southern Italy. All routine techniques for hemoglobin analysis yielded normal results with the exception of a slight increase in the Hb A2 value. The occurrence of a variant beta-globin was rapidly assessed by liquid chromatography mass spectrometric analysis and the abnormal chain purified by high performance liquid chromatography. The amino acid replacement Thr-->Ile at beta123 was determined by tandem electrospray mass spectrometric analysis of the tryptic digest of the variant beta chain. The corresponding DNA mutation was established as C-->T at the second position of codon 123 (ACC-->ATC) by polymerase chain reaction amplification techniques.

Adult↗
PubMed2001

Carcinogenic effects of polychlorinated biphenyls.

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of an important section of the Toxicological profile for polychlorinated biphenyls [ATSDR. 2000: Toxicological profile for polychlorinated biphenyls. Atlanta, GA: US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.] into the scientific literature. This article focuses on the carcinogenic effects of this group of synthetic organic chemicals (polychlorinated biphenyls) in humans and animals. Information on other health effects, toxicokinetics, mechanisms of toxicity, biomarkers, interactions, chemical and physical properties, potential for human exposure, and regulations and advisories is detailed in the profile.

Animals↗
PubMed2000

The mutation associated with Hb Peterborough [beta111(G13)Val-->Phe] originated from Southern Italy.

Hb Peterborough [beta111(G13)Val-->Phe], an unstable hemoglobin variant with low oxygen affinity, was first described in two patients of Italian origin. This paper reports the first observation of this variant in Campania, Southern Italy, in two unrelated patients suffering from mild anemia. The variant was separated from Hb A by cation exchange chromatography on a high performance liquid chromatographic system with an automated procedure that might be useful for diagnostic purposes. The amino acid replacement, Val-Phe at [beta111, was assessed by tandem electrospray mass spectrometry analysis, and the corresponding DNA mutation was established as G-->T at the first position of codon 111 (GTC-TTC) by polymerase chain reaction amplification techniques. A family study showed that the two original carriers of Hb Peterborough were members of the same family as the proband examined in this study. This finding, and the presence of a second unrelated family carrying Hb Peterborough in Campania, strongly suggests that the DNA mutation associated with this variant originated in Southern Italy.

Adult↗
PubMed1999

ATSDR evaluation of health effects of chemicals. VI. Di(2-ethylhexyl)phthalate. Agency for Toxic Substances and Disease Registry.

Di(2-ethylhexyl)phthalate (also known as DEHP, bis(2-ethylhexyl)phthalate, or BEHP; CAS Registry Number 117-81-7) is a widely-used plasticizer. It is found in numerous plastic articles, such as paints, inks, floor tiles, upholstery, shower curtains, footwear, plastic bags, food-packaging materials, toys, and medical tubing. Not surprisingly, DEHP appears at many waste sites. As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals that are of greatest public health concern at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priority List (NPL) sites. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of the bulk of ATSDR's profile for DEHP (ATSDR, 1993) into the mainstream scientific literature. An extensive listing of human and animal health effects, organized by route, duration, and endpoint, is presented. Toxicological information on toxicokinetics, biomarkers, interactions, sensitive subpopulations, reducing toxicity after exposure, and relevance to public health is also included. Environmental information encompasses physical properties, production and use, environmental fate, levels seen in the environment, analytical methods, and a listing of regulations. ATSDR, at the behest of Congress and therefore the citizenry, prepares these profiles to inform the public about site contaminants.

Biomarkers↗
PubMed1999

Hb Rainier [beta145(HC2)Tyr-->Cys] in Italy. Characterization of the amino acid substitution and the DNA mutation.

A high oxygen affinity hemoglobin variant was identified in a 53-year-old male patient from Napoli (Italy), suffering from pulmonary thromboembolism and polycythemia. A detailed structural characterization of the variant hemoglobin was carried out, both at the protein and DNA levels, by a combination of DNA sequencing and allele-specific amplification techniques with mass spectrometric procedures. The amino acid substitution was found to be Tyr-->Cys, and the corresponding DNA mutation was identified as A-->G at the second position of codon 145 of the beta chain. These variations indicated the presence of Hb Rainier. Haplotype analysis of DNA polymorphisms showed that the beta-globin gene from Hb Rainier was associated with haplotype II. Moreover, structural analyses provided direct identification of an intramolecular disulphide bridge joining the newly inserted beta145Cys with beta93Cys. This is the first report of the occurrence of Hb Rainier in Italy.

Adolescent↗
PubMed1997

Compound heterozygosity for Hb Lepore-Boston and Hb Neapolis (Dhonburi) [beta 126(H4)Val-->Gly] in a patient from Naples, Italy.

The simultaneous presence of two hemoglobin variants has been detected in a 14-month-old patient affected by thalassemia intermedia. The two variants were characterized by a combination of allele-specific amplification methods and mass spectrometric procedures carried out on isolated globins. These were identified as Hb Lepore-Boston and Hb Neapolis (also known as Hb Dhonburi) or beta 126 (H4)Val-->Gly. Hb Lepore-Boston is the most common hybrid variant detected in Campania and several cases of Hb Neapolis which causes a mild hypochromic microcytic anemia have been identified in this region in the last few years. This is the first report of a double heterozygosity involving Hb Lepore-Boston and Hb Neapolis.

Follow-Up Studies↗
PubMed1992

Clinical relevance of immunological dissection in T-ALL: a report on 20 cases with stem cell (CD7+, CD4-, CD8-, CD1-) phenotype.

In a prospective study on 44 cases of T-cell origin acute lymphoblastic leukemia, 20 patients were found to display an immature immunophenotype (CD7+, CD4-, CD8-, CD1-) and were classified as T-stem cell leukemia (T-SCL). Twenty-four patients expressed CD4 and/or CD8 antigens on their blast cells, designated T acute lymphoblastic leukemia (T-ALL). The T-SCL subset showed a significantly higher median age, a more frequent incidence of extramedullary leukemia, a morphology L1 in most cases, and a poor response to treatment in terms of either complete remission rate or median survival duration. In addition, significant differences between the two groups were found in evaluating the number of days of blast disappearance from peripheral blood, of CR achievement, and of neutrophils and platelets recovery. We conclude that T-SCL represents a distinct clinical entity, characterized by a poor response to ALL conventional chemotherapy. Alternative therapeutic approaches should be developed for patients suffering from this form of leukemia, to modify its severe prognosis.

Adult↗
PubMed1992

A randomized study of the efficacy of postconsolidation therapy in adult acute nonlymphocytic leukemia: a report of the Italian Cooperative Group GIMEMA.

The Italian Co-operative Group GIMEMA conducted a randomized trial in adult acute nonlymphocytic leukemia (ANLL) to assess the role of postconsolidation treatment. Of 448 evaluable patients entered into the study, 305 (68%) achieved a complete remission after a standard induction with daunorubicin and cytosine arabinoside (3 + 7; 2 + 5). Those in remission after a consolidation therapy including 4 courses of daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) were allocated to one of three arms: no treatment, conventional maintenance, or intensive postconsolidation therapy. The median disease-free survival (DFS) was 13 months, and the median survival was 14 months, with 26% surviving at 6.5 years. There was no difference in survival and in disease-free survival among the three postconsolidation arms. In conclusion our study, as others, suggests that the critical period of ANLL treatment is within the first 5-6 months.

Adolescent↗
PubMed1991

Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and Lymphocytes.

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that 111In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV. These findings suggest that: (i) DC, unlike TDL, are unable to recirculate from blood to lymph nodes through HEV; (ii) although gamma irradiation impairs TDL recirculation, it does not affect DC tissue distribution; and (iii) UV-B irradiation impairs both TDL and DC migration patterns. We conclude that the lack of capacity of irradiated TDL to home to lymph nodes is due to damage to cell surface homing receptors and that the failure of DC to home to the lymph node microenvironment is related to the absence of HEV homing receptors on their cell surface.

Animals↗
PubMed1991

Open noncontrolled multicenter long-term trial with ciclosporin in endogenous non-infectious uveitis.

The efficacy, tolerability and safety of low doses (5-7 mg/kg/day) of oral ciclosporin (CS) for treatment of endogenous uveitis resistant to conventional therapy were studied in an open, noncontrolled, multicenter long-term trial. CS was shown to be effective for patients with posterior or intermediate noninfectious uveitis; it limited the progression of the disease, decreased the number and severity of inflammatory relapses, and improved visual acuity while reducing signs of intraocular inflammation. Moreover, in corticodependent patients, a steroid-sparing effect was also obtained. At low doses and by means of the careful monitoring of safety parameters, the side effects (especially renal function impairment) were well controlled. Efficacy was maintained during long-term treatment.

Adult↗
PubMed1990

Myeloid antigen expression in adult acute lymphoblastic leukemia: clinicohematological correlations and prognostic relevance.

Fifty adult patients with acute lymphoblastic leukemia (ALL) were prospectively studied to determine the clinical and hematological relevance of surface immunophenotypes. Before treatment, blast cells were assayed for reactivity to monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. My antigens (CD13, CD33, and VIM2, singly or in combination) were demonstrated in 16 cases (32%) along with lymphoid specificities. Bone marrow and peripheral blood stains were classified according to French-American-British (FAB) Cooperative Group criteria and evaluated for myelodysplastic changes and azurophilic granules. Mean age of My+ patients was significantly higher. Furthermore, a greater number of My+ cases showed azurophilic cytoplasmic granules and acid ANAE positivity. FAB subtypes and myelodysplastic features did not significantly differ in the two groups analyzed, but patients with myelodysplastic abnormalities represented a significantly older age group. Response to treatment was comparable in My+ and My- cases, in terms of either complete remission rate or median survival duration.

Adult↗