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Biomedical subjects

P Carlier

Publications and source records attributed to P Carlier.

At least 19 recordsLinked to original sources
PubMed1996

High-dose chemo-radiotherapy followed by autologous Philadelphia chromosome-negative blood progenitor cell transplantation in patients with chronic myelogenous leukemia.

Twenty-three patients with chronic myelogenous leukemia in early chronic phase (ECP) and not previously treated with alpha-interferon (IFN-alpha) (10 patients), in ECP but pretreated with IFN-alpha (<12 months) (seven patients) and in late chronic phase (LCP) pretreated with IFN-alpha (>12 months) (six patients) underwent autografting with Philadelphia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patients), or partially/totally Ph-positive BPCs (three patients), previously mobilized during the early phase of recovery after aplasia induced by intensive chemotherapy. The conditioning regimen consisted of high-dose chemotherapy alone or followed by total body irradiation (TBI). Recombinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-alpha are alive and five of them are Ph-negative in the marrow after autografting. Six of seven patients autografted with Ph-negative BPCs in the group of ECP pretreated with IFN-alpha (<12 months) are alive and two of them are still Ph-negative in the marrow. In the same group, the only patient transplanted with partially Ph-positive BPCs, died of blastic transformation 2 months after reinfusion. Three patients (two patients autografted with Ph-negative BPCs and one patient with Ph-positive BPC) in the group of LCP pretreated with IFN-alpha >12 months are alive but Ph-positive after autografting. The other three patients of the same group died of procedure-related toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-alpha; 5/7 ECP pretreated with IFN-alpha and 2/6 LCP pretreated with IFN-alpha) of 23 autografted patients were treated with IFN-alpha +/- IL-2. Toxicities after autografting were mostly related to myelosuppression, particularly thrombocytopenia. All patients of the two groups pretreated with IFN-alpha developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreated with IFN-alpha developed febrile episodes. This is also probably due to the use of i.v. antibiotic and antimicotic prophylaxis when neutrophils were < or = 1 x 10(9)/l after autografting. Greater toxicity was observed in patients pretreated with IFN-alpha, being lethal in two cases in LCF. In conclusion, the "in vivo' manipulation approach employed in our institution is a safe procedure and it results in a high collection of Ph-negative cells in the blood if the cells are harvested: (1) in early chronic phase; (2) in early phase of recovery after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-alpha. The data presented here have shown encouraging trends in chronic phase of CML and offer new perspective for patients without an HLA-identical donor or for patients who do not respond to IFN-alpha.

Adult↗
PubMed1995

Intraoperative blood salvage (IOBS) in cardiac and vascular surgery.

The extensive application of IOBS has permitted a great reduction in the use of homoglous transfusion which presently represents the largest field of application of autologous systems. In cardiac and vascular surgery, IOBS is particularly useful to the goal of preventing the transmission of viral disorders and other adverse effects related to homologous transfusions. The apparatuses for IOBS may also be used to perform hemodilution and sequestration of a desired amount of platelet rich plasma. The appropriate usage of drugs in perioperative period and the promotion of hemostasis with IOBS are important costituents for the correct transfusional management of the patient. The feasibility and safety of IOBS is known and in expert hands it is an optimal method for the transfusional treatment of surgical patients.

Blood Transfusion, Autologous↗
PubMed1995

[Bilateral adrenal hemorrhage induced by stress. Radiological diagnosis. Apropos of a case].

Bilateral hemorrhage of the adrenal gland is a rare disease in adults. Although stress is often said to be the cause, it is rarely observed. The non specific clinical manifestations, and the absence of adrenal insufficiency demonstrate the importance of radiology. The diagnosis is made by ultrasonography and CT scan, which reveals an oval adrenal mass of high density that subsequently decreases in both size and density.

Adrenal Gland Diseases↗
PubMed1994

[Concentration of free intracellular magnesium in the myocardium of spontaneously hypertensive rats treated chronically with calcium antagonist or angiotensin converting enzyme inhibitor].

In this study, we determined a) whether chronic antihypertensive treatment could alter myocardial free intracellular magnesium concentrations, b) whether changes in magnesium concentration would correlate with resistance to anoxia of hypertensive rat hearts. Six-month old male spontaneously hypertensive (HT) rats (n = 11) were compared to rats from the same strain treated with a calcium channel antagonist, nitrendipine (60 mg/kg/j; n = 11) or with a converting-enzyme inhibitor, perindopril (2 mg/kg/j; n = 9) during three months. The hearts were perfused in retrograde isovolumic mode and submitted to a standardized anoxia-recovery protocol. Aortic perfusion pressure and left ventricular pressure were constantly monitored. P-31 NMR spectra were simultaneously recorded and allowed to quantify the changes in myocardial inorganic phosphate, phosphocreatine and ATP. The pH was derived from the chemical shifts of inorganic phosphate and phosphocreatine, and the free intracellular magnesium concentration from the alpha-beta chemical shifts of ATP. Both treatments lowered systolic blood pressure and reversed left ventricular hypertrophy, perindopril being slightly more efficient at the dose administered. Intracellular magnesium concentration, calculated from the P-31 NMR spectra, was 277 +/- 17 microM in the untreated hypertensive group, 311 +/- 15 microM in the nitrendipine group and 401 +/- 17 microM in the perindopril group (p < 0.001 versus untreated and nitrendipine). There was a significant correlation between intracellular magnesium concentration and left ventricular developed pressure at the early stage of post-anoxic recovery (r = 0.61; p < 0.01). P-31 NMR spectroscopy demonstrates an increase in myocardial free intracellular magnesium concentration following chronic administration of an angiotensin-converting enzyme inhibitor, perindopril, spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Excel: a new cell separator in its very first clinical application.

BACKGROUND: The evolution of technology has been one of the most interesting features that has accompanied thrombocytapheresis throughout the years. In this presentation we report on the preliminary results obtained with Excel, a third-generation cell separator that is presently in its early experimental phase. MATERIAL AND METHODS: So far only 15 thrombocytapheresis procedures, 2 of which of the single-needle type, were carried out on 15 healthy donors processing 4 liters of blood (2.8 liters in single needle). RESULTS AND CONCLUSIONS: The results were satisfactory since the average platelet yield was 4.7 x 10(11). The leukocyte contamination was 0.8 x 10(6) and the RBC contamination 0.4 x 10(7). The platelet efficiency per minute was 6.5 x 10(9), and the run time average 72 min. As to the quality of the product the very first results of platelet aggregation, relative to pre-apheresis, were 78% in response to ADP 6 microM; 106 and 102% in response to collagen 4.5 micrograms/ml and ristocetin 1.5 mg/ml, respectively. Essentially no platelet aggregates were found in the platelet products (Wu-Hoak ratio: 0.91).

Adult↗
PubMed1993

Donors thrombocytapheresis with last generation cell separators.

An exciting, fast moving and promising field remains the use of plasma-free synthetic medium for platelet storage (10, 11), that along with the potential for getting more plasma for therapeutic needs, might also improve the quality of stored platelets. Addition of acetate to solution, may be the way to obtain these results. An astonishing fact is that citrate remains the only anticoagulant for platelet collection, and remains as well the only real cause of donor discomfort during thrombocytapheresis.

Blood Donors↗
PubMed1993

Plasma exchange: the cost/benefit ratio and the critical revision of indications.

The number of conditions that can benefit from Plasma-Exchange (PE) continues to grow. We have recently added to the list the Cyclosporin-A induced hypertrygliceridemia and myoglobinuric acute renal insufficiency. Such as any therapeutic measure for PE, four evolutive phases can be recognized: the discovery and research, the confirmation of indications, the routine applications and the decline, when new more powerful tools are offered by culture or technology. We have participated in the first three phases during the last 20 years. Not necessarily all experiences were favourable. Nonetheless, we feel that, for the time being, a hemapheresis unit is an absolute necessity for a medium - sized hospital even if only therapeutic procedures are carried out. The phase four, decline of interest and applications, cannot be foreseen. Finally the ability of PE to shorten substantially the length of hospital stays along with the ease with which procedure can be performed on ambulatory patients, substantiate a favourable cost/benefit ratio for this therapeutic modality.

Humans↗
PubMed1993

The organization of the autotransfusion-perioperative blood salvage at San Martino Hospital.

Autologous transfusion is playing an important role in modern transfusion medicine. At San Martino hospital we use a combination of manual and mechanical techniques in order to improve autotransfusion procedures, control the hypertransfusion and avoid waste. Our autotransfusion program has determined a 55% reduction in the red cell concentrates used (from 42,000 in 1985 down to 19,400 in 1992). Proper training, cultural improvements and new applications on autotransfusion procedures will permit a better use of blood with less transfusion related complications, until a suitable substitute for blood will be available.

Blood Loss, Surgical↗
PubMed1993

Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group.

Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.

Adolescent↗
PubMed1993

Single-needle thrombo-cytapheresis with the Fresenius AS 104.

BACKGROUND: The Fresenius AS 104 cell separator has recently met some popularity in European apheresis units for the quality of the platelets obtained with the totally automated double-needle procedure. MATERIALS AND METHODS: Taking advantage of the machine's flexibility we have developed a new automated procedure for single-needle thrombocytapheresis (SNP). So far 61 SNP were carried out. From donors having a platelet precount of 2.74 x 10(5) an average of 3.8 x 10(11) cells were collected by processing 2.5 liters of blood in a run time of 83 min. RESULTS AND CONCLUSIONS: The leukocyte and erythrocyte contaminations were 2.7 x 10(7) and 3.5 x 10(7), respectively. Only 2 products did contain less than 3.5 x 10(11) platelets, and 7 procedures were complicated by minor signs of hypocalcemia. With minor modifications this SNP is presently offered on a routine basis to our platelet donors.

Adult↗
PubMed1992

Autologous and allogeneic bone marrow transplantation in acute myeloid leukemia in first complete remission: an update of the Genoa experience with 159 patients.

In the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy x 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was "purged" with in vitro technique, this review seems to confirm the importance of "in vivo" purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to draw final conclusions.

Adolescent↗
PubMed1992

Intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and acute lymphoblastic leukemia.

Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9 patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2 patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive conventional chemotherapy. During early recovery from marrow aplasia, when WBC reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4-8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6 patients lost the cytogenetic translocations, one patient died during aplasia, two patients did not have cytogenetic modifications and died in few weeks of leukemia and one patient out of six responding patients relapsed before transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2 patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/- Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission; all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It is concluded that intensive conventional chemotherapy employed in CML and ALL can lead to a precocious overshoot of cytogenetically normal BSC.

Adolescent↗
PubMed1991

Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation in hematological malignancies.

In the attempt to induce graft-vs-host disease (GVHD) in patients undergoing autologous bone marrow transplantation (ABMT) or blood stem cell transplantation (BSCT), 12 consecutive patients received cyclosporin A (CyA) post transplant. CyA was given at a dose of 1.5 mg/kg/day intravenously for 28 days, starting on the day of transplant. Histologically proven acute GVHD of the skin occurred in seven patients 9-14 days after ABMT and lasted 7-11 days. CyA-induced GVHD after ABMT resembles mild GVHD after allogeneic bone marrow transplantation (BMT). Although the preliminary data reported here show that it is possible to induce GVHD in patients undergoing ABMT, it is not yet known whether GVHD after ABMT will have an antitumor activity.

Adult↗
PubMed1991

Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation.

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion. RESULTS: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg. CONCLUSIONS: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion.

Animals↗
PubMed1991

Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A.

The expansion of the Philadelphia (Ph) chromosome positive clone in chronic myeloid leukemia (CML) may depend on its capacity to suppress the proliferation of Ph-negative stem cells, but this proliferative advantage might, in certain circumstances, be reversible. Various lines of evidence suggest that Ph-negative cells, albeit in a suppressed state, must still be present. As recently suggested, the expansion of 'putative' normal Ph-negative hemopoietic stem cells might have, in certain circumstances, a proliferative advantage over the Ph clone in CML. This suggests that the treatment of CML with intensive chemotherapy might allow the collection of Ph-negative hemopoietic cells in the early phase of recovery. Eight patients with acute phase chronic myelogenous leukemia (AP-CML) were treated with idarubicin, intermediate dose cytarabine and etoposide. During recovery from bone marrow aplasia, when the white blood cell count reached 0.3-1 x 10(-9), blood cells were collected with 2-5 (median 3) consecutive leukapheresis. In 5/8 patients, these peripheral cells were Ph-negative at the cytogenetic analysis. Moreover, in one case the polymerase chain reaction analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis was negative, further confirming that this approach may induce a very high degree of suppression of the Ph-positive clones. After complete recovery, these five patients were subsequently treated with high-dose etoposide, cyclophosphamide and total body radiation (10 Gy, single dose) followed by reinfusion of Ph-negative peripheral blood stem cells. All these patients received cyclosporine A post-autotransplant in an attempt to induce acute graft-versus-host-disease. Three of 5 patients remain in clinical and cytogenetic remission 5-15 months post-transplant. It is concluded that Ph-negative peripheral blood stem cells can be recovered from patients with AP-CML and used successfully to restore Ph-negative hemopoiesis after high dose therapy.

Adult↗