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Biomedical subjects

R Martinelli

Publications and source records attributed to R Martinelli.

At least 19 recordsLinked to original sources
PubMed2006

Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer.

BACKGROUND: We hypothesized that anemia could represent one of the major factors influencing the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before surgery for rectal cancer in three oncology/radiotherapy departments from June 1996 to December 2003. RESULTS: Three hundred and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26-88 years); male/female ratio was 184/133. Two hundred and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317 patients (76.3%). At univariate and multivariate analysis, only the hemoglobin (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a significant factor for disease-free survival. The role of the Hb level seemed to be confirmed further by the clinical downstaging obtained in approximately 55% of patients in group 2, in comparison with 35% of the patients achieving a significant downstaging in group 1. CONCLUSION: Our results indicated that anemia could represent an important parameter able to influence the outcome in patients receiving neo-adjuvant treatment of rectal cancer.

Adult↗
PubMed2006

Differential effects of egg albumen content on barn swallow nestlings in relation to hatch order.

In diverse animal taxa, egg mass variation mediates maternal effects with long-term consequences for offspring ontogeny and fitness. Patterns of egg mass variation with laying order differ considerably among birds, but no study has experimentally investigated the function of variation in albumen or yolk egg content in the wild. In barn swallows (Hirundo rustica), absolute and relative albumen mass increased with egg laying order. Experimental albumen removal delayed hatching, had larger negative effects on growth of late-hatched nestlings, and reduced nestling survival. Laying order positively predicted hatch order. Because nestling competitive ability depends on size, and albumen egg content influences hatchling size, present results suggest that by increasing albumen content of late eggs mothers reduce hatching asynchrony and enhance growth particularly of late-hatched nestlings. Thus, variation in albumen mass with laying order may function to mitigate the negative phenotypic consequences of hatching late in species that adopt a 'brood-survival' strategy.

Animals↗
PubMed2005

Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model.

BACKGROUND: Coexistence with harmless microorganisms such as lactobacilli, saprophytic mycobacteria and some helminths, throughout evolution, may have shaped the host immune system. Exposure to such organisms may have therapeutic benefits by triggering immunoregulatory mechanisms that control inappropriate immune responses to self, gut contents or allergens. OBJECTIVE: We determined whether treatment with Mycobacterium vaccae by gavage influences the host immune response both locally and systemically. We also investigated whether delivery by this route prevents severe symptoms of disease in a murine model of pulmonary allergic inflammation. RESULTS: A single intragastric administration of M. vaccae induced a transient increase in the production of IL-10 and IFN-gamma by mesenteric lymph nodes cells and splenocytes. In addition, in a mouse model of pulmonary allergic inflammation, a single treatment with M. vaccae by gavage not only diminished the total cellular infiltrate and the eosinophilic component induced by subsequent intratracheal allergen challenge, but also biased local and systemic cytokine production towards IL-10. Delivery of M. vaccae by gavage was as effective as subcutaneous treatment. CONCLUSION: This is the first report to suggest that heat-killed mycobacteria can down-regulate symptoms of allergic inflammation by the intragastric route. These data suggest an alternative route of treatment with M. vaccae for patients with allergic conditions.

Administration, Oral↗
PubMed2004

Cyclophosphamide in the treatment of focal segmental glomerulosclerosis.

Prednisone is the initial treatment of primary focal segmental glomerulosclerosis. However, when immunosuppressive agents in combination with steroids are used in the treatment of prednisone-dependent and prednisone-resistant patients the remission rate is variable. We report a long-term trial using cyclophosphamide (2.0 to 3.0 mg/kg body weight for 12 weeks) in combination with prednisone (1.0 to 2.0 mg/kg body weight), as compared with prednisone alone for the treatment of prednisone-resistant and frequently relapsing nephrotic syndrome and focal segmental glomerulosclerosis. Fifty-four patients (34 males and 20 females) with a diagnosis of idiopathic nephrotic syndrome and focal segmental glomerulosclerosis, followed-up for an average of 86.1 +/- 82.4 months, were evaluated. Complete remission occurred in 20.4% and partial remission in 14.8% of the patients treated with steroids and in 26.7 and 20.0% of the patients treated with cyclophosphamide + prednisone, respectively. Of the 24 prednisone-resistant patients treated with steroids in combination with cyclophosphamide, 33.3% obtained a complete/partial response. At the time of final evaluation, 25% of the patients treated with prednisone and 10.0% of those treated with prednisone in combination with cyclophosphamide had reached end-stage renal disease. Persistent nephrotic syndrome and progressive renal insufficiency were more frequently observed among the patients treated with prednisone alone (50.0 vs 33.3% and 33.3 vs 16.7%, respectively). The treatments were well tolerated and no patient experienced adverse reactions requiring discontinuation of medications. Although open-label and non-randomized, the present trial showed that cyclophosphamide is a reasonable choice for the treatment of primary focal segmental glomerulosclerosis and prednisone-resistant nephrotic syndrome.

Adolescent↗
PubMed2004

Comparative study of permanent interstitial prostate brachytherapy post-implant evaluation among seven Italian institutes.

BACKGROUND AND PURPOSE: The purposes of this multicentric study are (a) the evaluation of four different commercially available treatment planning systems (TPSs) and (b) to verify whether the dosimetric results are comparable, also when considering the inter-observer variabilities and the different scanning protocols used. This work is to be considered a first step to test the value of multicentric studies based on dosimetric evaluation of the quality of the implants. PATIENTS AND METHODS: Four different TPSs were used and the following tests were performed:Comparison of the parameters and mathematical algorithms used; comparison of the dose distributions generated by three different geometries of sources based on 32 dose-points on each source geometry. An octagonal geometric phantom was used to compare volume algorithms and dose-volume histogram (DVH) calculations (V150(Gy), V100(Gy), V50(Gy) and V25(Gy)). Comparison of the post-plan source distribution performed on a prostate-phantom implanted with (125)I seeds. A CT scan of the phantom was obtained at each participating center. Both the geometrical coordinates (with respect to the most caudal one), and the spread of the geometrical distribution, were calculated. The volumes included within different isodoses were also collected. Comparison of the post-plan source distribution performed on an actual patient. Post-plan V100% and D90(Gy) derived from seed distributions obtained by different operators were calculated, using the same target delineation. RESULTS: All the considered TPSs satisfied the AAPM dosimetric parameter recommendations. Point-dose examinations revealed differences smaller than 5%, except for one of the systems. Although the volume algorithm was not the same for all systems, no statistically significant difference was found in the volume measurements. The DVHs also presented differences smaller than 5%, except for one TPS. The distances between the seeds, based on the same CT images, showed a mean SD of 0.13 mm. The mean maximum difference of the position of each seed was 0.36 mm. The most significant errors were made in the cranio-caudal direction (mean maximal difference: 0.44 mm); here the size of the step between slices played an important role. The algorithm of source positioning of the different TPSs may also help explain this difference. The compiled DVHs showed differences smaller than 5%. Post-plans derived from different seed distributions showed a mild dependence upon operators. We obtained a mean value of 97.8 and 152.7 with a percentage of SD of 0.43 and 1.7, respectively, for V100% and D90(Gy). CONCLUSIONS: Three-dimensional (3D) geometric reconstructions of seed distributions are slightly dependent upon the operators and the scanning protocols have little effect on the dosimetric evaluation. Some relevant discrepancies were found between one of the TPSs and the other three if few sources were used; increasing the number of seeds those differences became less pronounced. Multicentric studies on the quality of prostate implants based on post-implant dosimetry are feasible, provided an accurate step-wise evaluation of the procedure be performed.

Aged↗
PubMed2004

Genetic variation in infestation with a directly transmitted ectoparasite.

Genetic variation in levels of parasitism of hosts is an underlying assumption of studies of coevolution, but few such estimates are available from the field. We studied genetic variation in the abundance of the chewing louse Hirundoecus malleus on its barn swallow host Hirundo rustica. These parasites are directly transmitted and a test of genetic variation of parasite abundance would thus provide a particularly strong test. The prevalence and the abundance of the chewing lice did not differ significantly between adult male and female hosts. The resemblance in parasite intensity of H. malleus of offspring and their parents was positive and highly significant, and an analysis of extra-pair paternity in the host allowed partitioning of this resemblance between genetic and common environment effects. There was no significant resemblance in parasite intensity between extra-pair offspring and their foster parents, although the resemblance remained for within-pair offspring. This provides evidence for the abundance of directly transmitted parasites having an additive genetic component. We found no evidence of common environment effects as parents did not resemble each other with respect to lice abundance.

Animals↗
PubMed2003

Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders.

In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn's disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg). This paper provides an overview of relevant work in each of these fields of medicine (though with emphasis on the allergic disorders), and concludes that the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are "old friends", because of their continuous presence throughout mammalian evolution. These organisms, which include saprophytic mycobacteria, helminths and lactobacilli, are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. Polymorphisms of components of the innate immune system such as TLR2 and NOD2 appear to define subsets of the population that will develop immunoregulatory disorders when living in the modern environment. A further role of the "old friends" and of the Treg that they induce might be to maintain the levels of regulatory IL-10 secreting macrophages and antigen-presenting cells, which are depleted in asthma and Crohn's disease. These concepts are leading to novel therapies based on harmless organisms or their components. Phase I/II clinical trials have yielded some statistically significant results, and phase II trials are in progress.

Adjuvants, Immunologic↗
PubMed2003

Measuring fast neutrons in Hiroshima at distances relevant to atomic-bomb survivors.

Data from the survivors of the atomic bombs serve as the major basis for risk calculations of radiation-induced cancer in humans. A controversy has existed for almost two decades, however, concerning the possibility that neutron doses in Hiroshima may have been much larger than estimated. This controversy was based on measurements of radioisotopes activated by thermal neutrons that suggested much higher fluences at larger distances than expected. For fast neutrons, which contributed almost all the neutron dose, clear measurement validation has so far proved impossible at the large distances (900 to 1,500 m) most relevant to survivor locations. Here, the first results are reported for the detection of 63Ni produced predominantly by fast neutrons (above about 1 MeV) in copper samples from Hiroshima. This breakthrough was made possible by the development of chemical extraction methods and major improvements in the sensitivity of accelerator mass spectrometry for detection of 63Ni atoms (refs 8-11). When results are compared with 63Ni activation predicted by neutron doses for Hiroshima survivors, good agreement is observed at the distances most relevant to survivor data. These findings provide, for the first time, clear measurement validation of the neutron doses to survivors in Hiroshima.

Copper↗
PubMed2003

Maternal antibodies but not carotenoids in barn swallow eggs covary with embryo sex.

Mothers influence their offspring phenotype by varying egg quality. Such maternal effects may be mediated by transmission of antibodies and antioxidants. Mothers should adjust allocation of maternal substances depending on embryonic sex because of differences in reproductive value, potentially dependent on paternal genetic effects as reflected by secondary sexual characters. We manipulated sexual attractiveness of male barn swallows (Hirundo rustica) and investigated maternal investment in eggs in relation to offspring sex. Mothers allocated more antibodies against a pathogen to eggs with a daughter than a son. However, concentration of antioxidants was independent of embryonic sex. Sex-dependent allocation was independent of paternal attractiveness. Thus, mothers adjusted allocation of substances to offspring in a complex manner, that may be part of a strategy of favouritism of daughters, which have larger mortality than sons. Such effects may have important consequences for secondary and tertiary sex ratios, but also for ontogeny of adult phenotype.

Animals↗
PubMed2002

Offspring sexual dimorphism and sex-allocation in relation to parental age and paternal ornamentation in the barn swallow.

We analysed the morphology of nestling barn swallows (Hirundo rustica) in relation to their sex, and laying and hatching order. In addition, we studied sex-allocation in relation to parentage, parental age and expression of a secondary sexual character of fathers. Molecular sexing was conducted using the sex chromosome-linked avian CHD1 gene. Sex of the offspring was not associated with laying or hatching order. None of nine morphological, serological and immunological variables varied in relation to offspring sex. Sexual dimorphism did not vary in relation to parental age and expression of a paternal secondary sexual character. The proportion of sons declined with brood size. Individual males and females had a similar proportion of sons during consecutive breeding years. The proportion of sons of individual females declined with age, but increased with the expression of a secondary sexual character of their current mate. The generalized lack of variation in sexual dimorphism among nestlings may suggest that barn swallows do not differentially invest in sons vs. daughters. Alternatively, male offspring may require different parental effort compared to their female siblings in order to attain the same morphological state. The lack of variation in offspring sexual dimorphism with paternal ornamentation suggests no adjustment of overall parental effort in relation to reproductive value of the two sexes. However, male-biased sex ratio among offspring of highly ornamented males may represent an adaptive sex-allocation strategy because the expression of male ornaments is heritable and highly ornamented males are at a sexual selection advantage.

Age Factors↗
PubMed2002

A feasibility study of a single event spectrometer based on semiconductor devices.

The electronics employed around particle accelerators can be disturbed or damaged because of single event effects (SEE). The most likely effect is the single event upset (SEU) which may affect all memory devices. In the case of high energy accelerators, SEUs are mostly produced by secondary charged particles generated by neutron interactions. The measurement of the energy and the lineal energy distribution of these neutron-induced charged particles was proposed. As a first approach, a commercial p-i-n photodiode was employed. This device was irradiated with thermal and monoenergetic fast neutrons. Some effects limiting the use of such a detector as a SEE spectrometer were observed, giving guidelines for the design of an application specific integrated circuit (ASIC). The possibility of creating a solid state microdosemeter by coupling the ASIC with a tissue-equivalent radiator is discussed. Moreover, the p-i-n photodiode covered with a hydrogenated plastic radiator may be employed as a proton-recoil spectrometer.

Dose-Response Relationship, Radiation↗
PubMed2002

Race and glomerulonephritis in patients with and without hepatosplenic Schistosomiasis mansoni.

BACKGROUND/AIMS: United States investigators have shown evidence of higher susceptibility to focal segmental glomerulosclerosis (FSGS) in blacks than in whites. This association between race and FSGS has not been assessed outside the US. The present study assesses the association between race and type of glomerulonephritis in a sample of Brazilian patients, taking into account the presence of the hepatosplenic form of Schistosomiasis mansoni (HSM). METHODS: Eighty patients with focal segmental glomerulosclerosis (FSGS) were compared to 50 with membranoproliferative glomerulonephritis (MPGN). The association between race (i.e. black versus white) and type of glomerulonephritis was adjusted for age, gender and HSM by logistic regression. RESULTS: Blacks were more likely than whites to have FSGS (as compared to MPGN), both among patients with HSM (odds ratio (OR) = 2.67; 95% confidence interval (CI) = 0.81 - 8.81) and without HSM (OR = 2.19; 95% CI = 0.79 - 6.05). After adjustment for age, gender and HSM, the odds of FSGS remained significantly greater for blacks (OR = 2.49; 95% CI = 1.05 - 5.95). CONCLUSION: The increased likelihood of FSGS in Brazilian blacks is consistent with findings from US patients. The association between race and type of glomerulonephritis was similar between patients with and without HSM. Future investigations should focus on the mediators factors that might explain these findings.

Adolescent↗
PubMed2001

Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity.

In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted hydroxylamines. The compounds were tested for their cytotoxic activity in vitro against H460 non-small lung carcinoma cell line, the activity being for 24 out of 37 compounds in the 0.01-0.3 microM range. A QSAR analysis indicated that lipophilicity is the main parameter correlated with cytotoxicity. Investigation of the DNA-Topo I-drug cleavable complex showed a rough parallelism between cytotoxicity and inhibition of Topo I. Persistence of the DNA cleavage after NaCl-mediated disruption of the ternary complex suggests that for the most potent compounds, e.g., 15, the cytotoxicity was at least in part related to stabilization of the complex, as also supported by the persistence of the DNA-enzyme complex in drug-treated cells. The in vivo antitumor efficacy of the most potent analogue (15) was evaluated in direct comparison with topotecan using human lung tumor xenograft models. In the range of optimal doses (2-3 mg/kg), the improved efficacy of 15 was documented in terms of inhibition of tumor growth and rate of complete response.

Animals↗
PubMed2001

The CC chemokine eotaxin (CCL11) is a partial agonist of CC chemokine receptor 2b.

Despite sharing considerable homology with the members of the monocyte chemoattractant protein (MCP) family, the CC chemokine eotaxin (CCL11) has previously been reported to signal exclusively via the receptor CC chemokine receptor 3 (CCR3). Using the monocyte cell line THP-1, we investigated the relative abilities of eotaxin and MCPs 1-4 to induce CCR2 signaling, employing assays of directed cell migration and intracellular calcium flux. Surprisingly, 1 microm concentrations of eotaxin were able to recruit THP-1 cells in chemotaxis assays, and this migration was sensitive to antagonism of CCR2 but not CCR3. Radiolabeled eotaxin binding assays performed on transfectants bearing CCR2b or CCR3 confirmed eotaxin binding to CCR2 with a K(d) of 7.50 +/- 3.30 nm, compared with a K(d) of 1.68 +/- 0.91 nm at CCR3. In addition, whereas 1 microm concentrations of eotaxin were able to recruit CCR2b transfectants, substimulatory concentrations of eotaxin inhibited MCP-1-induced chemotaxis of CCR2b transfectants and also inhibited MCP-1-induced intracellular calcium flux of THP-1 cells. Collectively, these findings suggest that eotaxin is a partial agonist of the CCR2b receptor. A greater understanding of the interaction of CCR2 with all of its ligands, both full and partial agonists, may aid the rational design of specific antagonists that hold great promise as future therapeutic treatments for a variety of inflammatory disorders.

Amino Acid Sequence↗
PubMed2001

Primary focal segmental glomerulosclerosis in children: prognostic factors.

To study the clinical course and the predictors of outcome in children and adolescents, 39 patients with nephrotic syndrome and primary focal segmental glomerulosclerosis (FSGS) were followed for a mean of 84.6 months. Thirty-six patients were treated with prednisone, either alone or in conjunction with cyclophosphamide. The clinical course was one of sustained remission in 4 patients, frequent relapse in 13, persistent nonnephrotic proteinuria in 5, and persistent nephrotic syndrome in 17; 2 patients had stable renal failure and 8 had progressive renal failure, 5 of them evolving to end-stage renal failure (ESRF). Resistance to prednisone was recorded in 76.6% of patients. The use of cyclophosphamide plus prednisone was of benefit in 42.8% of patients; 22.2% of the prednisone-resistant patients achieved remission of the nephrotic syndrome. A Kaplan-Meier analysis revealed a survival rate of 92% after 5 years, 86% after 10 years, and 76% after 15 years. Using both univariate and multivariate analysis, persistent nephrotic syndrome was associated with progression to ESRF and the remission of proteinuria with maintenance of renal function. As the outcome of the nephrotic syndrome in FSGS is significantly improved by remission of proteinuria, it is conceivable that immunosuppressive medication may be used in conjunction with prednisone in patients with steroid resistance.

Adolescent↗
PubMed2000

Better red than dead: carotenoid-based mouth coloration reveals infection in barn swallow nestlings.

Nestling birds solicit food from their parents by displaying their open brightly coloured gapes. Carotenoids affect gape colour, but also play a central role in immunostimulation. Therefore, we hypothesize that, by differentially allocating resources to nestlings with more brightly coloured gapes, parents favour healthy offspring which are able to allocate carotenoids to gape coloration without compromising their immune defence. We demonstrated that, in the barn swallow Hirundo rustica, (i) parents differentially allocate food to nestlings with an experimentally brighter red gape, (ii) nestlings challenged with a novel antigen (sheep red blood cells, SRBCs) have less bright gape colour than their control siblings, (iii) nestlings challenged with SRBCs but also provided with the principal circulating carotenoid (lutein) have more brightly coloured red gapes than their challenged but unsupplemented siblings and (iv) the gape colour of nestlings challenged with SRBCs and provisioned with lutein exceeds that of siblings that were unchallenged. This suggests that parents may favour nestlings with superior health by preferentially feeding offspring with the brightest gapes.

Animals↗
PubMed2000

Development of a murine orthotopic model of leukemia: evaluation of TP53 gene therapy efficacy.

The onco-suppressor gene TP53 has potential use in the gene therapy of many human cancers including leukemias. The latter indication derived from numerous experimental reports of p53-mediated suppressing effects on human and murine leukemia cells in vitro. However, few in vivo experiments have been performed, and those that have used a subcutaneous injection of p53-transduced leukemia cells. Thus, we developed an orthotopic leukemia model in adult, syngenic mice to evaluate the feasibility of TP53-mediated therapeutic approaches. We found that among other cells, v-src-transformed 32D myeloid progenitors induce leukemia when injected intravenously in syngenic mice. The resulting malignancy resembles the clinical manifestations of human acute myeloid leukemia because it is characterized by a massive invasion of bone marrow compartments, splenomegaly, generalized lymphadenopathy, and a macroscopic or microscopic infiltration of the kidneys, liver, and lungs. When these 32Dv-src cells were infected with a TP53-recombinant retrovirus before intravenous injection, we found a decreased mortality and, in those animals that develop leukemia, a drastic reduction of the generalized organ infiltration, suggesting that exogenous TP53 expression might be used for ex vivo bone marrow purging from leukemia cells.

Animals↗