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Biomedical subjects

M Battaglia

Publications and source records attributed to M Battaglia.

At least 91 records · Page 5Linked to original sources
PubMed1998

Autologous platelet transfusion in patients receiving high-dose chemotherapy and circulating progenitor cell transplantation for stage II/III breast cancer.

BACKGROUND AND OBJECTIVE: Concerns about the risk of transfusion therapy are driving towards new strategies which are designed to minimize exposure to allogeneic blood products. We aimed to find out whether it is possible to support the phase of thrombocytopenia following high-dose chemotherapy (HDC) and circulating progenitor cells (CPC) transplantation by autologous platelet concentrates (PC). DESIGN AND METHODS: PC were collected from 32 patients undergoing HDC and CPC transplantation for stage II/III breast cancer. A single plateletpheresis was performed at rebound after high-dose cyclophosphamide, when platelet count exceeded 250 x 10(9)/L. PC were cryopreserved in 5% DMSO after controlled-rate freezing and stored in liquid nitrogen. In vitro studies of cryopreserved platelets (aggregation, ATP release and change of mean platelet volume induced by EDTA) were performed. When platelet counts dropped below 20 x 10(9)/L following HDC (thiotepa 600 mg/m2, L-PAM 160 mg/m2) and CPC transplant (CD34+ cells > 5 x 10(6)/kg), PC were thawed in a 37 degrees C water bath, centrifuged to remove DMSO, resuspended in autologous plasma and reinfused within one hour. RESULTS: Large quantities of platelets were harvested in all patients (median 6.6 x 10(11), range 4.8-12.2). In vitro studies showed preserved platelet function as compared to both fresh platelets and standard PC. Twenty-eight out of 32 patients received autologous PC. At the time of transfusion most of the patients were febrile (> 38 degrees C) and had mucositis > G2. The median number of platelets reinfused was 3.8 x 10(11) (range 2.0-8.1) with a median loss during the freeze-thaw-wash procedure of 37%. Autotransfusion was able to maintain platelet count above 20 x 10(9)/L in most patients, with a corrected count increment > 7.5 in 20 cases. Four patients required one additional allogeneic transfusion, two because of a poor increment and two due to a late-occurring epistaxis. No side effects related to PC infusion were recorded. Sixteen control patients who received the same HDC and a similar number of CD34+ cells required a total of 17 allogeneic PC units (1 patient did not require platelet transfusion). INTERPRETATION AND CONCLUSIONS: Our data demonstrate that large doses of autologous platelets can easily be collected and safely administered to support the period of thrombocytopenia in patients undergoing HDC and CPC transplantation. Autologous PC in these patients can abrogate the risks deriving from allogeneic platelet transfusion.

Adult↗
PubMed1997

Multilineage long-term engraftment potential of drug-resistant hematopoietic progenitors.

Peripheral blood progenitor cells (PBPCs) are increasingly used instead of bone marrow for autologous or allogeneic transplantation. In this study PBPCs mobilized in cancer patients by chemotherapy and granulocyte-colony stimulating factor were collected by apheresis and first enriched by immunoaffinity removal of lineage positive cells. When these cells were exposed to both cyclophosphamide and taxol or cultured for 7 days in the presence of 5-fluorouracil, stem cell factor, and interleukin-3, 88% to 93% of the enriched PBPCs were killed and short-term clonogenic capacity in methylcellulose assays was lost, but week-5 cobblestone area-forming cell (CAFC) enrichment was higher than 10-fold in comparison to enriched PBPCs and higher than 700-fold in comparison to unmanipulated apheresis cells. After drug exposure, most of the progenitors displayed a CD34+, CD38-, multidrug-resistance (MDR+), Rhodamine 123 low, Hoechst 33342 low phenotype, and as few as 180 of these drug-resistant cells were able to generate a stable multilineage human hematopoiesis in sublethally irradiated immunodeficient mice. In these animals, the level of human hematopoietic engraftment was significantly increased by cotransplantation of irradiated cells from the human L87/4 stromal cell line. These observations are consistent with the functional isolation of a population of very early hematopoietic progenitors and might help to design new protocols for the removal of neoplastic cells from autografts.

Animals↗
PubMed1997

Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients.

We evaluated different culture conditions to obtain a lineage-selected proliferation of clonogenic megakaryocytic progenitors (MP). In low-density (LD) or CD34+ cell cultures, the best results were obtained in serum-free medium in the presence of megakaryocyte growth and development factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL-11, FLT-ligand, and macrophage inflammatory protein-1alpha. In paired studies, expansion of LD cells was less effective than expansion of CD34+ cells, and pre-enrichment of CD34+ cells using negative depletion of lineage-positive cells produced significantly larger quantities of MP than pre-enrichment using positive selection. MP proliferation peaked on day 7 in culture, and an 8- +/- 5-fold expansion of CD34+/CD61+ cells, a 17- +/- 5-fold expansion of colony-forming units-megakaryocytes, and a 58- +/- 14-fold expansion of the total number of CD61+ cells was obtained. In a feasibility clinical study, 10 cancer patients (8 with breast cancer and 2 with non-Hodgkin's lymphoma) undergoing autologous peripheral blood progenitor cell (PBPC) transplant received MP generated ex vivo (range, 1 to 21 x 10(5)/kg CD61 cells) together with unmanipulated PBPC. Eight patients received a single allogeneic platelet transfusion, whereas platelet transfusion support was not needed in 2 of the 4 patients receiving the highest doses of cultured MP. This result compares favorably with a retrospective control group of 14 patients, all requiring platelet transfusion support. Adverse reactions or bacterial contamination of cell cultures have not been observed. In conclusion, MP can be expanded ex vivo and safely administered to autologous transplant recipients. Further clinical trials will indicate the reinfusion schedule able to consistently abrogate the need for allogeneic platelet transfusion support in autologous transplantation.

Cells, Cultured↗
PubMed1997

Nimodipine on shuttle-box avoidance learning in mice: no impairment but slight improvement.

The dihydropyridine calcium channel antagonist nimodipine was tested in mice of CD-1, C57BL/6, and DBA/2 strains subjected to shuttle-box avoidance training. In contrast with some findings of other authors showing impairment of shuttle-box avoidance learning by low doses of the drug in rats, nimodipine given IP before each training session at doses of 0.25, 0.5, 1, 2.5, or 5 mg/kg never impaired avoidance acquisition in mice. On the contrary, one dose of nimodipine (1 mg/kg) significantly improved avoidance acquisition in mice of the DBA/2 strain. The drug failed to impair avoidance performance in DBA/2 mice even if given acutely in the middle (third session) or at the end (fifth session) of the training period. The results contradict studies showing cognitive impairment induced by calcium channel blockers, and may provide some limited evidence in support of improved cognitive function in normal animals, although this effect is much less evident than in aged or brain-damaged subjects.

Animals↗
PubMed1997

Prevention of amitriptyline-induced avoidance impairment by tacrine in mice.

The effects of two cognition enhancers on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box avoidance acquisition and in previously trained mice of the DBA/2 strain. The nootropic agent piracetam (50, 100 or 200 mg/kg, i.p.) had slight or no effect in mice receiving amitriptyline (5 or 10 mg/kg, i.p.). Conversely, the acetylcholinesterase inhibitor tacrine (0.5, 1, 2 or 3 mg/kg, i.p.) prevented the avoidance impairment induced by 5 mg/kg amitriptyline on shuttle-box avoidance acquisition as well as on a previously learned avoidance response. The avoidance disrupting action produced by 10 mg/kg of the antidepressant drug was not affected by the anticholinesterase drug. The preventing action of tacrine seems specifically related to the avoidance impairment induced by amitriptyline, since the acetylcholinesterase inhibitor did not reduce, but enhanced the avoidance impairing action of the neuroleptic chlorpromazine. Taken together, the results indicate that amitriptyline-induced avoidance impairment, and the related preventing action of tacrine, may be ascribed to drug effects on the performance of the avoidance response, rather than to interferences with learning processes.

Amitriptyline↗
PubMed1997

Collection of circulating progenitor cells after epirubicin, paclitaxel and filgrastim in patients with metastatic breast cancer.

The efficacy of high-dose chemotherapy (HDC) and circulating progenitor cell (CPC) transplantation in metastatic breast cancer (MBC) relies mainly on giving this treatment after a response to conventional induction chemotherapy has been achieved. For this reason an optimal mobilization regimen should be therapeutically effective while minimizing the number of leucaphereses required to support the myeloablative therapy. The combination of an anthracycline and paclitaxel in chemotherapy-untreated MBC has produced impressive response rates. We evaluated the CPC-mobilizing capacity of the combination epirubicin (90 mg m(-2)) and paclitaxel (135 mg m(-2)) followed by filgrastim (5 microg kg(-1) day(-1)) starting 48 h after chemotherapy administration in ten patients with MBC who were eligible for an HDC and CPC transplantation programme. Leucaphereses were performed by processing at least two blood volumes per procedure at recovery from neutrophil nadir when CD34+ cells in the peripheral blood exceeded 20 microl(-1). In most patients (six out of 10) more than 2.5 x 10(6) CD34+ cells kg(-1), a threshold considered to be sufficient for haematopoietic reconstitution, were collected with a single apheresis. In the remaining four patients an additional procedure, performed the following day, was enough to reach the required number of progenitors. These data suggest that the epirubicin-paclitaxel combination, besides being a very active regimen in MBC, is effective in releasing large amounts of progenitor cells into circulation.

Adult↗
PubMed1997

A new 'two step' procedure for 4.5 log depletion of T and B cells in allogeneic transplantation and of neoplastic cells in autologous transplantation.

To evaluate a new 'two step' method for purging T, B and neoplastic cells from hematopoietic progenitor cells (PC), PCs were collected by apheresis and some suspensions were deliberately contaminated with 2-5% breast cancer cells. PCs were first processed through CellPro columns for positive selection of cells that express CD34. After this first step, the mean CD34+ cell recovery was 68 +/- 12%, and CD34+ cell purity was 61 +/- 11%; CD3+ and neoplastic cell depletion were 2.1 +/- 0.4 and 1.9 +/0 0.4 logs, respectively. Cells were further processed through the StemSep device for direct depletion of T and B cells or of breast cancer cells. After the first and the second step, overall CD34+ cell recovery was 50 +/- 7%, T and B cell removal was 4.7 +/- 0.4 log and neoplastic cell purging was 4.4 +/- 0.3 log, ie significantly superior to methods described in the past.

Antigens, CD34↗
PubMed1997

Role of tumor cells contaminating the graft in breast cancer recurrence after high-dose chemotherapy.

One of the possible drawbacks to autologous stem cell transplantation in breast cancer (BC) patients is the potential for tumor contamination in the transplanted product. We present a patient with advanced disease who received high-dose chemotherapy (HDC) and PBPC support as consolidation therapy after achieving complete remission with standard-dose first-line treatment, and suffered recurrence of the disease 6 months after transplantation. Retrospective analysis revealed the presence of contaminating cells in the leukapheretic product, and clinical evidence suggested a role for these cells in the tumor relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

The structure of DSM-III-R schizotypal personality disorder diagnosed by direct interviews.

Confirmatory factor analysis techniques were applied to test how competing models (unifactorial, bifactorial, and trifactorial) could be used to explain the structure of schizotypal disorder as defined in DSM-III-R and DSM-IV. Subjects were 538 nonpsychotic psychiatric outpatients and a replication sample of 225 nonpsychiatric patients and control subjects, interviewed by clinicians using the Structured Interview for DSM-III-R Personality Disorders. The study found that the best-fit solution encompassed three factors: cognitive-perceptual, interpersonal, and oddness. Future studies may benefit from considering schizotypal personality disorder as composed of three factors that may indicate the existence of three underlying (dys)functional systems.

Adult↗
PubMed1997

"Stem cell candidates" purified by liquid culture in the presence of Steel factor, IL-3, and 5FU are strictly stroma-dependent and have myeloid, lymphoid, and megakaryocytic potential.

Berardi et al. (Science 1995; 267:105) reported recently that combined cytokine stimulation and antimetabolite treatment were able to isolate cells with characteristics of hemopoietic stem cells. Bone marrow (BM) low-density cells were cultured for 1 week in the presence of Steel factor (SF), IL-3, and the antimetabolite 5-FU. Following this approach one in 10(5) BM cells were purified. These cells showed no clonogenic potential in soft gel assays but presented a striking myeloid-lymphoid potential as long-term culture-initiating cells (LTC-ICs). We investigated this new "stem cell candidate." following a similar approach we purified one in 55,000/130,000 cells from cord blood and peripheral blood in mobilized cancer patients. These cells displayed no clonogenic potential in methylcellulose assays in the presence of different cytokine combinations and generated very few or no clonogenic progenitors in liquid cultures in the presence of cytokines. When seeded on layers derived from the murine BM stromal cell line M2-10B4, 38-86% of the cells purified using this approach generated multilineage progenitors acting as LTC-lCs. In a different series of studies, after 5-week culture on human BM stromal cell line L87/4 layers, cells were forced to selected lineage differentiation by culture in the presence of low concentrations of SF and high concentrations of lineage-specific cytokines such as Flt3-ligand (myeloid and pre-B cell differentiation), Tpo (megakaryocytic differentiation). IL-7, and IL-2 (pre-B and NK differentiation). After 12-day culture under these conditions, generation of myeloid, pre-B, megakaryocytic, and NK progenitors was assessed by immunohistochemistry, flow cytometry, and mRNA expression of CD7, 14, 19, 41b, S6, and 61. We conclude that this procedure for multilineage progenitor cell purification is simple and effective and could have major implications for gene transfer and stem cell transplantation.

Cell Lineage↗
PubMed1997

Human coronavirus polyadenylated RNA sequences in cerebrospinal fluid from multiple sclerosis patients.

Human coronaviruses, represented by the two prototype strains HCV-OC43 and HCV-229E, are important human respiratory pathogens, also associated with necrotizing enterocolitis. Two previous studies, one describing the electron microscopic observation of doughnut-shaped particles, resembling coronaviruses, in a perivascular inflammatory lesion of brain tissue taken at autopsy from a multiple sclerosis patient, and the other one reporting the isolation of coronaviruses from the brains of two multiple sclerosis patients, suggested the possible association between coronaviruses and human demyelinating diseases. We analysed polyadenylated RNAs extracted from cerebrospinal fluid of twenty randomly selected multiple sclerosis patients and ten patients with other neurological diseases (medullary atrophy, Parkinson's disease, polyneuropathy, senile dementia, headache and toxic polyneuropathy) by reverse transcription and polymerase chain reaction searching for HCV-OC43 and HCV-229E sequences. By hybridization analysis of amplification products, we detected HCV-OC43 polyadenylated RNAs in ten specimens of patients with multiple sclerosis. Furthermore, we found positive hybridization signals for HCV-OC43 in the other neurological diseases, except for the toxic polyneuropathy specimen. Positivity for HCV-229E was observed in seven specimens of multiple sclerosis cerebrospinal fluid; one headache cerebrospinal fluid and the medullary atrophy specimen also resulted positive for HCV-229E. Moreover, using a solid phase technique, we report for the first time the sequence of a cDNA fragment derived from RNA extracted from cerebrospinal fluid of multiple sclerosis patient, belonging to the open reading frame which codes for the HCV-OC43 nucleoprotein N. Furthermore, cDNA sequences revealed the presence of a mixed viral population.

Coronavirus↗
PubMed1997

[Quantitative assessment of pulmonary emphysema with computerized tomography. Comparison of the visual score and high resolution computerized tomography, expiratory density mask with spiral computerized tomography and respiratory function tests].

CT is the most accurate method to detect pulmonary emphysema in vivo. We compared prospectively two different methods for emphysema quantitation in 5 normal volunteers and 20 consecutive patients with chronic obstructive pulmonary disease (COPD). All subjects were submitted to function tests and HRCT; three scans were acquired at preselected levels during inspiration. The type and extent of pulmonary emphysema were defined, using the time-honored visual score system, by two independent observers under blind conditions. Disagreements were subsequently settled by consent. All subjects were also examined with expiratory spiral CT, using a density mask program, at two different cut-off levels (-850, -900 HU). Visual score and expiratory spiral density mask values (-850 HU) were significantly correlated (r = 0.86), but the visual extent of emphysema was always higher than shown by expiratory spiral CT. The emphysema extent assessed with both CT methods correlated with the function result of expiratory airflow obstruction and gas diffusion impairment (visual score versus forced expiratory volume in one second: r = -0.81, versus single breath carbon monoxide diffusion: r = -0.78. Spiral expiratory density mask -850 HU versus forced expiratory volume in one second: r = -0.85, versus single breath carbon monoxide diffusion: r = -0.77). When -900 HU was used as the cut-off value for the expiratory density mask, the correlation with single breath carbon monoxide diffusion worsened (r = -0.56). Visual score and expiratory density mask -850 HU gave similar results and permitted COPD patients to be clearly distinguished from normal controls (p < 0.01). Residual lung volume, measured with expiratory spiral CT correlated significantly with residual volume measured with the helium dilution technique (r = 0.66), but CT values were always higher than function results. We believe the true residual volume should lie somewhere in between the CT value and the function results with the helium dilution technique and conclude that the extent of pulmonary emphysema can be confidently assessed with CT methods. Finally, the simple visual score may be as reliable as such highly sophisticated new methods as the spiral expiratory density mask. Expiratory studies offer new insights into different normal and abnormal features of COPD and respiratory impairment.

Aged↗
PubMed1997

Imaging of small airways disease, with emphasis on high resolution computed tomography.

Bronchioles are the airways less than 2-3 mm in diameter. Normal bronchioles cannot be reliably detected by means of high resolution computed tomography (HRCT). Nevertheless, in pathological cases, bronchiolar lesions can be identified by taking into account direct and indirect signs. On radiological grounds, bronchiolar lesions can be classified into four groups, on the basis of HRCT findings: 1) prevailing nodular opacities and "tree in bud" pattern; 2) consolidations or ground-glass opacities; 3) mosaic oligosemia with expiratory air-trapping; and 4) mixed cases. In this review, we present the main radiological and HRCT findings in four different entities, representing the more typical cases of bronchiolar pathology; bronchiolitis obliterans; bronchiolitis obliterans with organizing pneumonia; diffuse panbronchiolitis; and respiratory bronchiolitis with associated interstitial lung disease. HRCT sometimes allows a precise diagnosis of bronchiolar pathology; however, more often, it permits only a range of hypotheses to be advanced. More importantly, it allows a precise localization for biopsy procedures and an exact follow-up after institution of therapy. In normal subjects, less than 1% of the whole bronchial tree is visible on the standard chest radiograph. HRCT offers a good insight and invaluable information. New techniques, such as volumetric HRCT with sliding-thin-slab maximum- and minimum-intensity projections (MIP and minip) could represent an important additional tool in the evaluation of small airways disease.

Bronchiolitis↗