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L Bigi

Publications and source records attributed to L Bigi.

At least 19 recordsLinked to original sources
PubMed2006

Ex vivo expansion of umbilical cord blood CD34 cells in a closed system: a multicentric study.

BACKGROUND AND OBJECTIVES: The Dideco 'Pluricell System' is a CE-marked medical device allowing haematopoietic stem cell (HSC) expansion. It comprises a kit of cGMP cytokines and reagents, a closed-cell expansion chamber and a cell-washing set. We tested the system in a multicentric study by expanding CD34(+) cells from eight fresh umbilical cord blood (UCB) samples. MATERIALS AND METHODS: During culture, the mean nucleated cell (NC) count, the mean CD34(+) cell count, fold expansion, viability and apoptosis were measured. Clonogenic assays and immunophenotypical characterization were performed on days 0, 7 and 12. On the expanded cellular product, in three cases cell genotyping, endotoxin level and mycoplasma detection (by polymerase chain reaction) were performed. RESULTS: The mean CD34(+) cell expansion on days 7 and 12 was sevenfold and 12-fold respectively and the mean NC expansion was 69-fold and 180-fold. The mean NC viability on day 12 was 96.9% (94.4-99.1). After 12 days, granulocyte-macrophage colony-forming units (GM-CFU) showed a 20-fold increase: a slight increase in CD34(+) cell apoptosis was observed during culture. In all of three cases neither chromosomal alterations nor mycoplasma contamination was detected. No significant endotoxin levels were detected after expansion. CONCLUSIONS: The device allows the ex vivo expansion of NC and CD34(+) cells in a closed system. The expanded cellular product is a mixture of progenitors (CD34(+) cells) and differentiated (mainly myeloid and megakaryocytic) cells. To reduce cell apoptosis, more frequent cell feeding during culture should be tested.

Antigens, CD34↗
PubMed2005

Evaluation of ex vivo expansion and engraftment in NOD-SCID mice of umbilical cord blood CD34+ cells using the DIDECO "Pluricell System".

The Dideco "Pluricell System" is a commercially available closed device composed of an expansion chamber and a kit of certified reagents that allow haematopoietic stem cell expansion. We have expanded seven umbilical cord blood (UCB) samples following the manufacturer's instructions; two groups of irradiated NOD-SCID mice have been transplanted with expanded and nonexpanded cells from the same UCB, and bone marrow was analysed for the presence of human cells. Average UCB volume was 61.6+/-8.8 ml; mean nucleated cell content was 1090.5+/-189.9 x 10(6). Percentage and number of CD34+ cells were 0.37+/-0.13% and 3.9+/-1.2 x 10(6). After separation, CD34+ cell purity was 82+/-11%. Mean number of inoculated cells was 760 000; mean NC and CD34+ fold expansion at 12 days was 230.4+/-91.5 and 21.0+/-11.9. Both groups of mice showed successful engraftment: the percentage of human cells was higher in the group receiving expanded cells (3.4+/-2.01%) compared to the group receiving nonexpanded cells (1.5+/-0.66%) (P<0.00018, Mann-Whitney test). The cell population obtained after 12 days expansion consisted mainly of myeloid and megakaryocytic progenitors. The CD34+ antigen reached the maximum expression level at day 12 (7.5+/-2.0%). Analysis of lineage-markers for human myelomonocytic, megakaryocytic, B, T, CD34 and erythroid cells, gave evidence that all the lineages were represented in the marrow of transplanted mice.

Animals↗
PubMed2001

Erythrocyte-mediated delivery of dexamethasone in patients with chronic obstructive pulmonary disease.

Human erythrocytes from ten patients with chronic obstructive pulmonary disease (COPD) were loaded with increasing amounts of dexamethasone 21-phosphate and were re-infused into the original donors. Drug-loaded erythrocytes acted as circulating bioreactors, converting the non-diffusible dexamethasone 21-phosphate into the diffusible dexamethasone. Pharmacokinetic analyses on these patients showed that a single administration of drug-loaded erythrocytes was able to maintain detectable dexamethasone concentrations in blood for up to seven days. This continuous release of dexamethasone was paralleled by the suspension of beta2-agonist and oral corticosteroid treatments by all of the patients. Thus dexamethasone 21-phosphate-loaded erythrocytes are safe carriers for corticosteroid analogues and are a useful alternative to frequent oral or inhaled drugs in elderly patients with COPD.

Aged↗
PubMed2001

[Splenectomy for hematologic disease. Mini-invasive versus traditional technique].

BACKGROUND: This study aimed to compare the safety, efficacy and clinical benefits of laparoscopic splenectomy (LS) to open splenectomy (OS) in patients with hematologic disorders. METHODS EXPERIMENTAL DESIGN: prospective study; SETTING: II Department of Surgery, Santa Maria Nuova Hospital, Reggio Emilia and III Department of Surgery, Santo Spirito Hospital Pescara; PATIENTS: 48 consecutive adult patients underwent splenectomy; 30 patients under-went LS and 18 OS. Perioperative characteristics, outcomes, complications and costs were comparatively analyzed. RESULTS: Mean age was 35.3 years in the LS group, and 40.8 in the OS group. Mean spleen size was 11.7 cm in the LS group and 15.2 cm in the OS group. Accessory spleens were found in 5 patients in the LS group and in 4 patients in the OS group; 4 conversions to laparotomy occurred in the LS group. A total of 4 complications occurred in 3 patients of the LS; 9 complications occurred in 5 patients of OS group. Mean surgical time was 141.5 minutes for LS and 89.7 minutes for OS (p<0.005). Mean postsurgical stay was 5.8 days in the LS group and 8.5 days in the OS group (p<0.005). Response rates were similar in both groups. CONCLUSIONS: LS is comparable to OS in terms of efficacy and safety and it is associated with a shorter hospital stay. LS should become the technique of choice for treatment of intractable benign hematologic disease.

Adult↗
PubMed1998

Erythrocyte engineering for drug delivery and targeting.

A new procedure for the encapsulation of non-diffusible drugs into human erythrocytes was developed. With as little as 50 ml of blood and by using a new apparatus, it was possible to encapsulate a variety of biologically active compounds into erythrocytes in 2 h at room temperature and under blood-banking conditions. The process, which is based on two sequential hypotonic dilutions of washed red cells followed by concentration with a haemofilter and resealing of red cells, allows a 35-50% cell recovery and approx. 30% encapsulation of added drugs. The resulting processed erythrocytes have a normal survival in vivo and can be modified further, with the same apparatus, to increase their recognition by tissue macrophages to perform as a drug-targeting system. The new equipment designed and built for this procedure was named 'Red Cell Loader'.

Cell Membrane Permeability↗
PubMed1987

Tricarboxylic acid cycle intermediates in chronic renal failure.

In 21 uraemic subjects not yet requiring dialysis, the serum values of citrate, fumarate, oxalacetate and malate were significantly increased, so that the sum of the concentrations of the TCA-cycle intermediates were increased threefold compared to that of 18 control subjects. The replenishment of TCA intermediates could, in theory, occur by several anaplerotic reactions, mainly those catalysed by pyruvate-carboxylase and malic enzyme. The overall pattern detected in uraemic patients is similar to that observed in rat skeletal muscle during exercise, in which increased acetyl CoA has been found.

Adult↗
PubMed1986

Foreign bodies of the biliary tract. Endoscopic management.

In the period 1978-1984, 23 patients underwent endoscopic intervention for foreign bodies of the biliary tract. The patients are subdivided into three groups: the first group consists of 11 cases in which the foreign bodies were suture threads, either simple or as a nidus for gallstones; the second group consists of six patients with a sump syndrome of the biliary tract; the third group includes six patients who retained drainage tubes or stents after a biliary tract operation. In our series, endoscopic extraction was performed as a first-choice procedure. The high success rate may favor endoscopy as a low-morbidity, low-mortality approach and as an alternative to a relaparotomy.

Biliary Tract↗
PubMed1983

No relationship between acetate and hypotension in a standard dialysis schedule.

Plasma acetate (PA) kinetics was analysed in two groups of patients on regular dialysis treatment (RDT). The first group presented frequent symptomatic hypotension (SHY), the second did not experience SHY during RDT. The parameters examined showed no difference between the two groups. Seven patients of the first group were then switched to bicarbonate dialysis. SHY rate and blood pressure changes did not significantly differ between the two methods of treatment.

Acetates↗
PubMed1982

Pharmacological data and technical feasibility of intraperitoneal 5-fluorouracil administration.

Via a surgically implanted Tenckhoff catheter, 5-fluorouracil was intraperitoneally administered to patients with malignant disease confined to abdominal space. Treatment was well tolerated without local complications. Peritoneal and plasmatic drug levels were measured, showing that: 1) peritoneal drug levels declined as a first order function; 2) plasmatic levels were very close to those reported for continuous i.v. administration, but peritoneal concentrations were much higher (log 1 to 3); 3) concentration x time product had a peritoneum: plasma ratio ranging from 120 to 1350. The hypothesized role of intraperitoneal 5-fluorouracil administration and the questions still to be answered are summarized.

Aged↗
PubMed1979

Long-term use of a "stable" bicarbonate containing dialysate.

We present an original method for the preparation of "stable" dialysate containing 35 mEq/l of bicarbonate. The dialysate was utilized with 4 patients for periods ranging from 4 months to 1 year according to a short-term recirculated dialysis schedule in closed circuit (20-40L) (2-2 1/2 hrs) on alternate days. Preliminary results are reported here with respect to the tollerance of the dialytic run and correction of the acid-base balance equilibrium. The clinical tollerance is excellent despite high dehydration rates even in patients particularly sensitive to ultrafiltration. The acidosis correction would seem to be much better with bicarbonate than with traditional dialysis. The difference is even higher if we consider the brevity of the dialysis. During the bicarbonate dialysis we do not observe any fall of the PCO2 or significant difference in PO2 in the patient's blood. The correction of acidosis probably causes the normalization of pre-dialytic potassiemia in spite the "net" removal of K with short dialysis is considerably less.

Acidosis↗
PubMedDate not supplied

A novel protocol that allows short-term stem cell expansion of both committed and pluripotent hematopoietic progenitor cells suitable for clinical use.

To obtain long-term engraftment and hematopoiesis in myeloablated patients, the cell population used for hematopoietic reconstitution should include a sufficient number of early pluripotent hematopoietic stem cells (HSCs), along with committed cells from the various lineages. For this purpose, the small subset of CD34+ cells purified from different sources must be expanded ex vivo. Since cytokines may induce both proliferation and differentiation, expansion would provide a cell population comprising committed as well as uncommitted cells. Optimization of HSC expansion methods could be obtained by a combination of cytokines able to sustain renewal of pluripotent cells yet endowed with poor differentiation potential. We used variations of the combinations of cytokines described by Brugger et al. [W. Brugger, S. Heimfels, R. J. Berenson, R. Mertelsmann, and L. Kanz (1995) N. Engl. J. Med. 333, 283-287] and Piacibello et al. [W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta (1997) Blood 89, 2644-2653] to expand UCB CD34+ cells and monitored proliferation rate and phenotype after 14 days of culture. Several hematopoietic lineage-associated surface antigens were evaluated. Our data show that flt3L and thrombopoietin in combination with IL-3, while sustaining a high CD34+ proliferation rate, provide a relatively low enrichment in very early uncommitted CD34+/CD38- cells. Conversely, in the absence of IL-3, they are less effective in inducing proliferation yet significantly increase the number of CD34+/CD38- cells. A combination of the above protocols, applied simultaneously to aliquots of the same sample, would allow expansion of both committed and pluripotent HSC. This strategy may represent a significant improvement for clinical applications.

ADP-ribosyl Cyclase↗