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Biomedical subjects

D Morelli

Publications and source records attributed to D Morelli.

At least 19 recordsLinked to original sources
PubMed2006

Soil radon monitoring in the NE flank of Mt. Etna (Sicily).

Soil radon has been monitored at a fixed location on the northeastern flank of Mt. Etna, a high-risk volcano in Sicily. The aim of this study was to evaluate the effects of the recent volcanic activity on soil radon concentration. Continuous radon measurements have been performed since July 2001. While comparison between the trend in in-soil radon concentration and the acquired meteorological series (temperature, humidity and pressure) appear to confirm a general seasonal correlation, nevertheless particular anomalies suggest a possible dependence of the radon concentration on volcanic dynamics.

Journal Article↗
PubMed2005

Prognostic factors in multidisciplinary rehabilitation treatment in multiple sclerosis: an outcome study.

The aim of this outcome study was to evaluate the effectiveness and prognostic factors of inpatient multidisciplinary rehabilitation treatment in patients with multiple sclerosis (MS). We analysed 230 consecutive inpatients with MS admitted to an MS rehabilitation ward who followed an individualized, goal-oriented, multidisciplinary rehabilitation program. Every patient was submitted to a neurological examination and evaluated by means of Kurtzke's Expanded Disability Status Scale (EDSS), with its functional systems (FS), Barthel Index (BI) and the Rivermead Mobility Index (RMI). We observed an effectiveness (percentage of potential improvement achieved during rehabilitation) of nearly 16% on BI and 8% on RMI, corresponding to an improvement in 124 patients (54%) on BI and 113 patients (49%) on RMI. Basal EDSS (beta = -0.32, P <0.001), cognitive status (beta = -0.15, P <0.05) and disease duration (beta = -0.13, P <0.05) were negatively associated with effectiveness of treatment on BI (adjusted R2 = 0.176), whereas effectiveness on RMI was correlated only with the EDSS score (beta = -0.34, P <0.001, adjusted R2 = 0.113). In the logistic regression analysis, the absence of severe sphincteric disturbances was correlated with the probability of improvement on BI that was nearly twice as high (OR =2.25, 95% CI 1.24-4.08) as that of other patients. Moreover, patients without severe cognitive deficits showed a similar probability (OR =2.37, 95% CI 1.05-5.33) of improvement on RMI. The results of this study provide further evidence that intensive multidisciplinary rehabilitation in MS is effective in the majority of MS patients and that early treatment may favour functional recovery.

Activities of Daily Living↗
PubMed2001

Topical administration of a doxorubicin-specific monoclonal antibody prevents drug-induced mouth apoptosis in mice.

One of the most severe side effects of anti-tumour chemotherapy is mucositis due to drug toxicity for rapidly dividing cells. We show here that anti-DXR monoclonal antibodies can prevent DXR-induced damage. Indeed, apoptosis, confined to the proliferative compartment of the basal mucosa, observed in the tongue of DXR-treated mice was completely inhibited by topical application of the anti-DXR antibodies.

Administration, Topical↗
PubMed2001

Mobility status after inpatient stroke rehabilitation: 1-year follow-up and prognostic factors.

OBJECTIVES: To evaluate the stability of mobility status achieved by stroke patients during hospital rehabilitation treatment over time and to identify reliable prognostic factors associated with mobility changes. DESIGN: Follow-up evaluation in consecutive first-ever stroke patients 1 year after hospital discharge. Multiple logistic regressions were used to analyze increases and decreases in Rivermead Mobility Index (RMI) scores (dependent variables) between discharge and follow-up. Independent variables were medical, demographic, and social factors. SETTING: Rehabilitation hospital. PATIENTS: A cohort of 155 patients with sequelae of first stroke, with a final sample of 141. MAIN OUTCOME MEASURES: Mobility status at 1-year follow-up, as measured by the RMI, and odds ratios (OR) for improvement and decline in mobility. RESULTS: Functionally, 19.9% improved the mobility levels achieved during the inpatient rehabilitation treatment; levels of 42.6% worsened. Patients with global aphasia (OR = 5.66; 95% confidence interval [CI], 1.50-21.33), unilateral neglect (OR = 3.01; 95% CI, 1.21-7.50), and age 75 years or older (OR = 5.77; 95% CI, 1.42-23.34) had a higher probability of mobility decline than the remaining patients. Postdischarge rehabilitation treatment (PDT), received by 52.5% of the final sample, was significantly and positively associated with mobility improvement (OR = 5.86; 95% CI, 2.02-17.00). Absence of PDT was associated with a decline in mobility (OR = 3.73; 95% CI, 1.73-8.04). CONCLUSIONS: In most cases, mobility status had not yet stabilized at hospital discharge. PDT was useful in preventing a deterioration in mobility improvement achieved during inpatient treatment and in helping increase the likelihood of further mobility improvement.

Activities of Daily Living↗
PubMed2001

Post-stroke depression, antidepressant treatment and rehabilitation results. A case-control study.

The aim of this study was to assess the specific influence of poststroke depression (PSD) on both basal functional status and rehabilitation results. We performed a case-control study in 290 stroke inpatients, matched for age (+/-1 year) and onset admission interval (+/-3 days) and divided in two groups according to the presence (PSD+) or absence (PSD-) of PSD. All PSD+ patients were treated with antidepressants (AD), mainly with fluoxetine. PSD+ patients, despite similar severity of stroke, showed greater disability in coping with activities of daily living (ADL) on admission and greater disability both in ADL and mobility at discharge than PSD- patients. Although both groups exhibited similar average functional improvement during rehabilitation, PSD- patients were nearly twice as likely to show excellent recovery both on ADL and mobility as PSD+ patients (OR = 1.95, 95% CI = 1.01-3.75 and OR = 2.23, 95% CI = 1.14-4.35, respectively). All AD drugs improved depressive symptoms. Few relevant side effects were observed: fluoxetine was discontinued in 2 patients because of insomnia and in 2 patients because of nausea; paroxetine was stopped in 1 patient because of nausea and dry mouth. Our results confirm the unfavorable influence of PSD on functional outcome, despite pharmacological treatment.

Activities of Daily Living↗
PubMed2000

Early versus delayed inpatient stroke rehabilitation: a matched comparison conducted in Italy.

OBJECTIVE: To assess the specific influence of onset-admission interval (OAI) on rehabilitation results. DESIGN: A case-control study in consecutive stroke inpatients, enrolled in homogeneous subgroups, matched for age (within 1 year) and Barthel Index (BI) score at admission, and different for OAI to the rehabilitation ward. The short OAI group began rehabilitation treatment within the first 20 days from stroke, medium OAI group between days 21 and 40, and long OAI between days 41 and 60. SETTING: Rehabilitation hospital. PATIENTS: One hundred forty-five patients with sequelae of first stroke. MAIN OUTCOME MEASURES: Efficiency (average increase in BI per day), effectiveness (proportion of potential improvement achieved during rehabilitation) of treatment, and percentage of low- and high-response patients, calculated on BI, were evaluated. Odds ratios (ORs) of dropouts and of poor and excellent therapeutic response were also quantified. RESULTS: The short OAI subgroup had significantly higher effectiveness of treatment than did the medium (p < .05) and the long OAI groups (p < .005). Beginning treatment within the first 20 days was associated with a significantly high probability of excellent therapeutic response (OR = 6.11; 95% confidence interval [CI], 2.03-18.36), and beginning later was associated with a similar risk of poor response (OR = 5.18; 95% CI, 1.07-25.00). On the other hand, early intervention was associated with a five times greater risk of dropout than that of patients with delayed start of treatment (OR = 4.99; 95% CI, 1.38-18.03). The three subgroups were significantly (p < .05) different regarding the percentage of low and high responders. CONCLUSION: Our results showed a strong association between OAI and functional outcome.

Aged↗
PubMed1999

High level antibody response to retrovirus-associated but not to melanocyte lineage-specific antigens in mice protected against B16 melanoma.

Mice vaccinated with Mycobacterium tuberculosis Ag38 gene-transduced B16 melanoma cells showed significant protection from intravenous challenge with parental B16 melanoma cells. No cytotoxic T-cell activity was found against melanoma cells, although the endogenous presence of the mycobacterial gene induced a preferential Th1 response. After immunization, a low serological response against melanoma cells was detected, while a high titer of antibodies directed to parental B16 cells, mainly of IgG2(a) isotype, was found in protected mice after challenge. These antibodies exhibited complement-dependent cytotoxicity against melanoma cells in vitro, while in vivo, used in passive immunization, they induced a decrease in a number of experimental B16 lung metastases. Most of the antibodies were directed against endogenous murine leukemia viruses. No reactivity against melanocyte lineage-specific antigens was observed. In particular, no reactivity was found in sera from protected mice against tyrosinase-related protein 2 (TRP-2), either stably expressed in a non-melanoma cell line or obtained by in vitro transcription-translation, or against tyrosinase, TRP-1 and gp100 antigens immunoprecipitated from B16 cells. Thus, in the B16 murine model, the presence of dominant viral antigens induces a very strong humoral response that might be protective and may inhibit or mask the presence of minor clonotypes.

3T3 Cells↗
PubMed1999

Inhibition of fibronectin-activated migration of microvascular endothelial cells by interleukin-1alpha, tumour necrosis factor alpha and interferon gamma.

The effect of interferon gamma (IFN) and the inflammatory cytokines tumour necrosis factor alpha (TNF) and interleukin 1alpha (IL-1) on micro- and macrovascular endothelial cell (EC) proliferation and migration was analysed. Whereas both micro- and macrovascular EC were growth-inhibited in response to the aforementioned cytokines, only microvascular EC were sensitive to TNF, IL-1 and IFN as inhibitors of fibronectin-activated cell migration. In addition, because microvascular EC play a crucial role in angiogenesis, and the formation of new capillaries depends upon the presence of angiogenic polypeptides, we evaluated the synthesis of fibroblast growth factor (FGF) type 1 and 2, Vascular Endothelial Growth Factor (VEGF) and Hepatocyte Growth Factor (HGF) in our system. Both micro- and macrovascular EC produce large amounts of FGF-2, which is mainly localized in the nucleus, and almost undetectable levels of FGF-1. In addition, the two cell types synthesize notable levels of VEGF and no HGF. Whether these findings are relevant to the different in vivo functions of EC residing different districts remains the focus of additional studies.

Cell Division↗
PubMed1998

Segregation of type 1 cytokine production in human peripheral blood lymphocytes: phenotypic differences between IFN-gamma and IL-2-producing cells in the CD8+ T cell subset.

T cell clones are classified as type 0, 1 or 2 depending on the lymphokines they produce. However, it has remained unclear whether single cells of a given type produce one or several cytokine species. Flow cytometric analysis of peripheral blood lymphocytes (PBL) obtained from 20 healthy donors for the production of the type 1 cytokines IFN-gamma and IL-2 revealed very few cells that co-expressed both cytokines independently of the mitogenic stimulus used for PBL activation. Similarly, kinetic studies of cytokine synthesis indicated a low percentage of IFN-gamma/IL-2 double-positive T cells at all time points. Reverse transcription-PCR analysis of sorted IL-2- and IFN-gamma-positive T cells showed the presence of IL-2- or IFN-gamma-specific mRNA only in those cells expressing the corresponding cytokine. This segregation of the two type 1 cytokines was lost in long-term cultured T cells and in T cell clones. A high percentage of cells expressing only IL-2 or IFN-gamma was observed even when the production of these cytokines was evaluated on CD4- and CD8+ subsets. Moreover, in some healthy individuals, IFN-gamma and IL-2 production by CD8+ T cells was related to CD8+ expression levels and cell size, i. e. IL-2-expressing cells were generally smaller with more intense CD8+ staining as compared with IFN-gamma-producing T cells. These data indicate that activated T lymphocytes are strongly committed in vivo to produce IFN-gamma or IL-2 and emphasizes the independent regulation of the two cytokine genes.

CD8-Positive T-Lymphocytes↗
PubMed1998

Post-stroke rehabilitation: an economic or medical priority? Current issues and prospects in light of new legislative regulations.

The aim of this study was to evaluate: 1) whether the reduction in duration of in-patient rehabilitation imposed by the Italian Ministry of Health's circular of 29/6/95 has been accompanied by a decline in the results achieved; and 2) whether the system of basing payments on diagnosis related group (DRG) criteria is capable of correctly evaluating differences in post-stroke clinical pictures. The study involved 461 of 497 patients consecutively admitted between 1991 and 1996 for rehabilitation after a first stroke. The average duration of hospitalisation for the period 1995-1996 was significantly shorter (p<0.001) than that of the previous years; at the same time, there was a significant increase (p<0.05) in the number of poor responders in both neurological and functional (mobility) terms. Furthermore, the early discharge after 60 days of the 1995-1996 patients compromised the stabilisation of recovery and led to a subsequent functional decline. It is therefore hoped that the current regulations will be revised and that payments based on a functional related group (FRG) criterion will be introduced.

Aged↗
PubMed1998

Anti-tumor immunity induced by murine melanoma cells transduced with the Mycobacterium tuberculosis gene encoding the 38-kDa antigen.

The Mycobacterium tuberculosis Ag38 gene, which encodes a highly immunogenic protein, was cloned into a retroviral vector in-frame with the leader and the transmembrane portion of the nerve growth factor receptor, and transduced into murine melanoma cell line B16-B78. Significant protection was observed in mice immunized with the transduced melanoma cells and subcutaneously challenged with parental melanoma cells since only 20% of mice developed tumors. Necroscopy of mice immunized with the transduced melanoma cells revealed dramatic inhibition of experimental metastases induced by intravenous (i.v.) inoculation of parental melanoma cells. Moreover, vaccination with transduced cells significantly prolonged survival of mice challenged i.v. with parental melanoma cells. These data indicate that the presence of the mycobacterial 38-kDa protein greatly enhances immunological recognition of structures expressed by the parental melanoma cells. Comparison of Th1 and Th2 responses in mice immunized with parental melanoma cells versus mice receiving the transduced cells revealed a clear predominance of Th1 responses when the Ag38 protein was endogenously expressed. This transduction approach may represent a promising immunotherapeutic strategy for the treatment of cancer patients.

Animals↗
PubMed1998

Daily low-dose subcutaneous recombinant interleukin-2 by alternate weekly administration: antitumor activity and immunomodulatory effects.

A phase II clinical trial of subcutaneous recombinant Interleukin 2 (rIL-2) given by 5 days pulses followed by a 9 days rest has been performed in patients affected by renal cell carcinoma, malignant melanoma and colorectal cancer. A total of 25 patients entered the study, completed at least six courses of treatment, and were evaluable for toxicity and response to treatment. This schedule of subcutaneous rIL-2 was well tolerated and no World Health Organization grade 3 side effects were observed. A 33.3% response rate was recorded in patients affected by renal cell carcinoma, although no major responses were achieved in patients with malignant melanoma and colorectal cancer. A durable increase of natural killer activity retained by poeripheral blood mononuclear cells was demonstrated in these patients and was paralleled by increased serum levels of interferon gamma and tumor necrosis factor a without changes of circulating interleukin-1d. It is concluded that this schedule of pulse administration of subcutaneous rIL-2 has antitumor activity in renal cell carcinoma and produces durable biomodulatory effects.

Adult↗
PubMed1998

Evaluation of the balance between angiogenic and antiangiogenic circulating factors in patients with breast and gastrointestinal cancers.

Angiogenesis is a critical determinant of tumor growth. Tumor cells produce or induce angiogenic molecules that act specifically on endothelial cells (ECs) but also release angiostatic molecules. Thus, tumor angiogenesis represents a net balance between positive and negative regulators of neovascularization. Sera from patients with breast or gastrointestinal cancers were evaluated for their capacity to selectively modulate the proliferation of human umbilical vein ECs; sera from 15 of 78 (19%) breast cancer patients and 8 of 53 (15%) gastrointestinal cancer patients induced human umbilical vein EC growth, whereas sera from 4 of 78 (5%) breast cancer patients and 1 of 53 (2%) gastrointestinal cancer patients inhibited EC proliferation. Growth-stimulatory sera were significantly more frequent among postmenopausal (14 of 53) than premenopausal (1 of 25) breast cancer patients; inhibitory activity was observed in 3 of 25 premenopausal patients versus 1 of 53 postmenopausal individuals. The half-life of serum-stimulating and -inhibiting factors seemed to differ, because stimulatory activity but not inhibitory activity was decreased at 5 days after surgery. The levels of vascular endothelial growth factor were elevated in about 45% of patients with growth-stimulatory sera, whereas the serum inhibition of EC growth was found to be due, at least in part, to high levels of soluble thrombospondin.

Breast Neoplasms↗
PubMed1997

Intratibial injection of an anti-doxorubicin monoclonal antibody prevents drug-induced myelotoxicity in mice.

With few exceptions, the major limit to high-dose chemotherapeutic treatments is the severity and duration of drug-induced myelosuppression. We have recently developed a monoclonal antibody, MAD11, which reacts with the potent anti-tumour antibiotic doxorubicin and other anthracyclines. To protect directly pluripotent stem cells and cells of the haematopoietic microenvironment in the bone marrow against doxorubicin cytotoxicity, the monoclonal antibody MAD11 was injected into the tibial bone of mice before chemotherapeutic treatment. All mice pretreated intratibially with MAD11 and injected with 14 mg kg(-1) body weight of doxorubicin survived, whereas 41% of mice treated with doxorubicin alone died. At a higher dose of doxorubicin (18 mg kg(-1)), early mortality (first 6 days) was similar in the groups, but no deaths were observed thereafter in the intratibially MAD11-treated group, whereas most of the mice treated with doxorubicin alone died. Data obtained in mice injected with P388 leukaemia cells showed that the intratibial injection of MAD11 did not compromise the anti-tumoral activity of doxorubicin. Moreover, the administration of the anti-doxorubicin monoclonal antibody before chemotherapeutic treatment effectively reduced apoptosis induced by doxorubicin in the bone marrow cells. These data suggest the usefulness of monoclonal antibodies against chemotherapeutic drugs in the local protection of bone marrow without influencing the anti-tumour properties of the drug.

Animals↗
PubMed1996

Oral administration of anti-doxorubicin monoclonal antibody prevents chemotherapy-induced gastrointestinal toxicity in mice.

Gastrointestinal mucositis is a common and painful condition that afflicts a proportion of cancer patients receiving chemotherapeutic drugs including anthracyclines, and it has become the dose-limiting toxicity for a number of chemotherapeutic regimens. The murine monoclonal antibody MAD11 recognizes the anthracycline doxorubicin, and systemic administration of this antibody in mice treated with doxorubicin was found previously to prevent the toxic effects of the drug. The purpose of this study was to determine whether gastrointestinal toxicity associated with doxorubicin can be reduced by oral administration of anti-doxorubicin MAD11 in mice. Our experiments show that orally administered MAD11 antibodies: (a) are essentially not absorbed in the blood circulation since less than 0.5% of protein-associated radioactivity was recovered from blood samples; (b) reduce the extent of doxorubicin-induced apoptosis in murine intestinal crypts, as determined by labeling strand breaks with modified nucleotides in an enzymatic reaction; and (c) reduce the body weight loss in mice treated with 12 mg/kg body weight of doxorubicin and decrease the early mortality in mice treated with 16 mg/kg body weight. This type of treatment may be useful in preventing anthracycline-induced gastrointestinal mucositis in cancer patients.

Administration, Oral↗
PubMed1996

Shedding of the 67-kD laminin receptor by human cancer cells.

The 67-kD laminin receptor (67LR) is a cell membrane-associated molecule exhibiting high affinity for the basement membrane glycoprotein, laminin. While export of the 67LR toward the extracellular matrix has been recently suggested by electron microscopy studies, there is to date no evidence of shedding of the 67LR from cells. Using two monoclonal antibodies directed against the 67LR, we developed a double-determinant radioimmunoassay that demonstrates that the 67LR is released from cancer cells into the culture medium. The shed molecule exhibited the same apparent molecular weight as that of the membrane-associated 67LR, suggesting that no proteolytic cleavage is involved in the process. Furthermore, we demonstrate that the 67LR is not anchored to the membrane through a glycolsyl-phosphatidylinositol bridge. However, the observation that lactose increased the release of 67LR suggests that a lectin-type interaction is involved in the cell membrane association of this laminin binding protein and the cell surface. Interestingly, the released 67LR recovered after HPLC gel filtration was found free as well as associated to high molecular weight complexes. The free 67LR retained its ability to bind to the cell surface. Our study is the first demonstration that the 67LR is effectively shed by cancer cells. The released free 67LR could play an important role in modulating interactions between cancer cells and laminin during tumor invasion and metastasis.

Antibodies, Monoclonal↗