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Biomedical subjects

A M Ferrer

Publications and source records attributed to A M Ferrer.

14 recordsLinked to original sources

CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that frequently first presents in the skin.

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is an aggressive and rare preculsor hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to affect elderly patients, who usually present with skin lesions but often have a disseminated disease, including bone marrow involvement. Although the lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a relationship to plasmacytoid dendritic cells. Because of the rarity of this disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.

Aged↗

Cerebral hemodynamic effects of 7.2% hypertonic saline in patients with head injury and raised intracranial pressure.

The aim of the present study was to investigate the acute effects of 7.2% hypertonic saline (HS) on intracranial pressure (ICP), cerebral and systemic hemodynamics, serum sodium, and osmolality in 14 patients with moderate and severe traumatic brain injury (Glasgow Coma Scale < or =13) and raised ICP (>15 mm Hg) within the first 72 h postinjury. After CO2 reactivity and autoregulation were tested, each patient received a 15-min infusion of 7.2% HS (1,232 mEq/L, volume 1.5 mL/kg). ICP, serial hemodynamics, cerebral blood flow (CBF) estimated from cerebral arteriovenous oxygen content difference (AVDO2), and laboratory variables, including serum osmolality, electrolytes, urea, and creatinine were collected before infusion (T0) and at 5, 30, 60, and 120 min after (T5, T30, T60, T120). Urine output was measured 2 h before infusion and at T120. While CO2 reactivity was preserved in all patients, autoregulation was preserved in only four. ICP decreased to about 30% of base line (p = 0.0001) during the whole study period. During the first hour after infusion, cerebral perfusion pressure (p< or =0.04) and cardiac index (CI; p< or =0.01) increased, while systemic vascular resistance index fell (p< or =0.05). Heart rate increased (p< or =0.04) during the first 30 min. Pulmonary artery occlusion pressure (PAOP) increased (p = 0.004) at T5. There were no significant changes in mean arterial blood pressure (MABP), urine output, and estimated CBF. A significant positive correlation (r = 0.75; p = 0.02) between ICP and serum osmolality was found at T5. The administration of 7.2% HS in patients with traumatic brain injury significantly reduces ICP without significant changes in relative global CBF (expressed as 1/AVDO2), increases CI and transiently increases PAOP, without changing MABP and urine output. The correlation between changes in osmolality and ICP supports the hypothesis that HSS may in part decrease ICP by means of an osmotic mechanism.

Adult↗

Latency and reactivation of JC virus in peripheral blood of human immunodeficiency virus type 1-infected patients.

JC virus (JCV) acts as an opportunistic virus in immunocompromised human immunodeficiency virus type 1 (HIV-1)-infected patients. The role of peripheral blood cells in central nervous system invasion, before the onset of progressive multifocal leukoencephalopathy (PML), remains controversial. In order to clarify JCV latency or reactivation status in peripheral blood, 72 HIV-1-infected patients were studied, together with 7 HIV-1-positive PML patients and 50 blood donors. Blood leukocytes, plasma, and B lymphocytes were investigated by two complementary DNA amplification procedures within the early T and late VP1 JCV genes and two reverse transcription techniques for the detection of corresponding early transcripts and mRNAs. JCV DNA was detected in 40.3% of the HIV-1-infected patients but only 8% of the blood donors (P < 0.001). Leukocytes represented 82.7% of the positive samples, but plasma from 12 patients (41.4%) contained JCV DNA. B lymphocytes seemed to be involved in the natural history of JCV but did not represent the unique cell target. JCV DNA was intermittently found in blood, and JCV mRNAs for VP1 capsid protein were detected exclusively in one PML patient. Such observations demonstrate that JCV, when detected in blood, does not undergo active multiplication. They support the JCV hematogenous spread hypothesis, but do not indicate any direct link between peripheral virus and dissemination in the central nervous system at the time of immunodepression.

AIDS-Related Opportunistic Infections↗

Peripheral blood progenitor cell transplantation in 118 patients with hematological malignancies: analysis of factors affecting the rate of engraftment.

We retrospectively studied the factors affecting the rate of hematopoietic reconstitution (HR) in 118 patients with hematological malignancies who underwent peripheral blood progenitor cell (PBPC) transplantation at a single institution. The patients received a median number of 6.6 x 10(8) nucleated cells/kg corresponding to 9.5 x 10(4) (0.5-578) CFU-GM/kg and 6.8 x 10(6) (0.2-161) CD34-positive cells/kg. The median number of days to reach 500 polymorphonuclear cells/mm3 and 50,000 platelets/mm3 was 12.5 (6-93) and 14.5 (6-440) days, respectively. No patient died from infection during the aplastic phase. By multivariate analysis, we found that the dose of CFU-GM infused was the only factor that significantly affects the HR rate (p < 0.0001). Moreover, patients with acute myelogenous leukemia or those transplanted after busulfan or total-body irradiation conditioning regimens had a slower engraftment (p < 0.08). These results could lead to identifying patients who need growth factors posttransplantation and/or the reinfusion of "back-up" marrow together with PBPC.

Actuarial Analysis↗

Malignant infiltration of peripheral nerves in the course of acute myelomonoblastic leukaemia: neuropathological study of two cases.

Two patients suffering from acute myelomonoblastic leukaemia developed clinical evidence of peripheral nerve involvement. In both cases, a peripheral nerve biopsy revealed endoneurial cellular infiltrates which were identified as leukaemic cells by immunocytochemistry. Ultrastructural studies showed mainly axonal damage. Moreover, in one patient, a few features of active demyelination were also observed.

Action Potentials↗

Collection of peripheral blood stem cells in multiple myeloma following single high-dose cyclophosphamide with and without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF).

High-dose cyclophosphamide (HD-CY; 7 g/m2) was administered to patients suffering from high risk multiple myeloma (MM). The safety of this procedure, the recirculation and collection of peripheral blood stem cells (PBSC) and the effect of rhGM-CSF and HD-CY were studied. Group I patients (n = 21) were treated with HD-CY alone. Group II patients (n = 10) received 5 micrograms/kg/day rhGM-CSF iv after HD-CY. Neutropenia was shorter in group II (p = 0.01). In group II, the number of circulating colony forming units (CFU-GM) after 14 days was correlated with the number of circulating CFU-GM after 7 days (r = 0.85, p < 0.0001) and with the number of CD34+ cells (r = 0.839, p = 0.01). The total number of mononuclear cells (MNC) and CFU-GM collected per patient was two and seven-fold higher, respectively, in group II (p = 0.01 and p = 0.03). Recovered MNC and CFU-GM were 1.7 and 7-fold higher, respectively, in group II (p = 0.01 and p = 0.004). Our data show that HD-CY is an efficient means of collecting functional PBSC in MM. We suggest that rhGM-CSF is able to further enhance this yield in MM.

Adult↗

von Willebrand factor bound to glycoprotein Ib is cleared from the platelet surface after platelet activation by thrombin.

We recently reported that after activation of human platelets by thrombin, glycoprotein (GP) Ib-IX complexes are translocated to the surface-connected canalicular system (SCCS) (Blood 76:1503, 1990). As GPIb is a major receptor for von Willebrand factor (vWF) in platelet adhesion, we have now examined the consequences of thrombin activation on the organization of vWF bound to GPIb on the platelet surface. Studies were performed using monoclonal or polyclonal antibodies in either immunogold staining and electron microscopy (Au-EM) or in flow cytometry. When unstirred platelet-rich plasma was incubated with ristocetin, bound vWF was located by Au-EM as discrete masses regularly distributed over the cell surface. Platelets from a patient with Glanzmann's thrombasthenia, lacking GPIIb-IIIa complexes, gave a similar pattern, confirming that this represented binding to GPIb. That ristocetin was not precipitating vWF before their binding to the platelets was shown by the detection of similar masses on the surface of platelets of a patient with type IIB von Willebrand disease. Experiments were continued using washed normal platelets incubated in Tyrode-EDTA, the purpose of the EDTA being to limit the surface expression of endogenous vWF after platelet stimulation. Under these conditions, platelets were treated with ristocetin for 5 minutes at 37 degrees C in the presence of increasing amounts of purified vWF. This was followed by incubation with thrombin (0.5 U/mL) for periods of up to 10 minutes. Flow cytometry showed a time-dependent loss in the surface expression of vWF bound to GPIb and these changes were confirmed by Au-EM. In particular, immunogold staining performed on ultrathin sections showed that the bulk of the vWF was being cleared to internal membrane systems. Surface clearance of vWF during thrombin-induced platelet activation is a potential mechanism for regulating platelet adhesivity.

Antibodies↗

[Technique for automating HLA-DR typing].

Two types of anti-class II coated magnetic beads were compared for the use in isolation of B lymphocytes from whole blood. The HLA DR typing was performed in parallel after separation of the cells by the rosette technique. The depletion was monitored by Flow cytometry using CD2 and CD20 antibodies. Typing was performed using classic lymphocytotoxicity test of Propidium-Iodide-Carboxyfluorescein diacetate fluorescence. The results were scored with an ordinary microscope or by photometric evaluation. These techniques lead to simplification in cell isolation from small amounts of blood with an important gain of time and a less subjective interpretation of DR phenotyping was until now long and difficult.

Antigens, CD↗

The influence of cryopreservation on activity and surface markers of lymphokine-activated killer cells.

Ficoll-separated and monocyte-depleted mononuclear cells isolated from normal leukapheresis products were cryopreserved. These cells were incubated with or without 1,000 U/ml of recombinant interleukin-2 (rIL-2) for 4 days, and their lymphokine-activated killer (LAK) and natural killer (NK) activities were measured. IL-2 activation induced a significant increase in the expression of the CD25 antigen. There was no change in CD2, CD3, CD4, CD8, CD16, CD56 and CD57 cell marker expression. Cryopreservation did not induce any change in the membrane antigen expression and in the lymphocyte subsets. The NK activity was well preserved and the decrease of LAK activity of IL-2-activated cells after cryopreservation was not significant. In contrast, cells activated before cryopreservation had a significantly lower cytotoxic activity and the number of cells expressing the IL-2 receptor was also significantly reduced. However, the decrease of CD56 expression was not significant. CD25 expression seemed to be proportional to the LAK activity of the cells. This study demonstrated that cryopreserved lymphocytes, after 4 days of culture with rIL-2, could be as active and could express the CD25 and CD56 cell surface markers in the same manner as fresh LAK cells.

Antigens, CD↗

Characterization of liver-associated natural killer cells in patients with liver tumors.

The existence of a marginal lymphocyte population in rat liver sinusoids has already been demonstrated using the sinusoidal lavage method. We used the same technique to study the lymphocyte population in human liver obtained ex vivo after partial hepatectomy for benign or malignant tumors and compared it with peripheral and portal blood lymphocyte populations. Percentages of lymphocyte surface phenotypes were evaluated by flow cytometry. The lymphocyte population obtained from human liver is mainly made up of CD56+ (35%) cells. This percentage is three times greater than that found in peripheral and portal blood. Two-color flow cytometry analysis showed that within the CD56+ liver cell population, at least three distinct subsets could be found: (a) CD3+/CD56+/CD16-; (b) CD3-/CD56+/CD16-; and (c) CD3-/CD56+/CD16+. Although these subsets were also present in peripheral and portal blood, the percentage distribution was completely different because most CD56+ cells in peripheral and portal blood belonged to the CD3-/CD56+/CD16+ subset. These results show the existence of a heterogeneous natural killer cell population in human livers with tumors. The functional significance of this heterogeneity still needs to be explained.

Adult↗

[Identification of HLA B27 antigen by flow cytometry].

Cytofluorograph analysis after immunofluorescence with monoclonal antibodies can be useful for various antigens identification on the surface of cell membrane. This technic is described for antigen HLA B27 identification. This HLA antigen is known indeed to be linked to rhumatismal diseases. The fluorescence histograms obtained, allow to differentiate easily subjects which have HLA B27 phenotype and subjects which are HLA cross linked.

Antibodies, Monoclonal↗

[Lymphoproliferative syndrome with granular lymphocytes of CD8+ phenotype: a clonal pathology with a chronic course].

The syndrome of CD8 hyperlymphocytosis with neutropenia is a heterogeneous disorder ranging from reactive benign state to neoplastic pathology. The prognosis for LGL (Large Granular Lymphocyte) leukemia depends likely on its phenotype:-NK phenotype, extremely poor prognosis and rapidly fatal-T phenotype (CD8+), chronic disease with slow progression. Here, we report four cases of CD8+ hyperlymphocytosis with neutropenia, which are CD2+/-, CD3+, CD4-, CD8+, CD16-, CD56+/-, CD57+ phenotype. These lymphocytic proliferations were associated with clonal rearrangement of T-cell receptor b gene. In two cases, characteristic blood hyperlymphocytosis appeared only after splenectomy, but retrospective bone marrow analysis showed that the CD8+, CD57+ lymphocyte proliferation previously existed. These lymphocytes had a low natural killer activity against K562 cell line. HTLV1 proviral sequence was not integrated in leukemic cell DNA. This monoclonal pathology has a chronic clinical course, with a thirteen year evolution in one case. Splenectomy did not correct neutropenia but allowed the control of hemolytic anemia and auto-immune thrombocytopenia in one case.

Adult↗

[Transient neurological syndrome after spinal hyperbaric bupivacaine: a new case].

A 47-year-old woman underwent hysteroscopy and removal of an endometrial polyp because of irregular, acyclic bleeding of 6 months' duration. The procedure was carried out under spinal anesthesia. No adverse events occurred during puncture or surgery, or in the immediate postoperative recovery period. Recovery from the sensory and motor block was normal. Twenty-four hours after surgery gluteal and lower limb pain and paresthesia developed, with no sensory or motor deficit. The symptoms suggested transient neurological syndrome. This syndrome has been defined by pain in the lower limbs, buttocks, thighs and calves after uncomplicated spinal anesthesia and full recovery from the sensorimotor block during the immediate postoperative period (first 24 hours). The condition is self-limiting and does not leave permanent neurological sequelae. Recent studies have demonstrated biochemical and anatomical changes that provide a structural basis for this clinical entity. According to this literature, transient neurological syndrome might be a mild expression of local anesthetic toxicity. Recent findings show that the initial injury to the nerve cell membrane, induced by high concentrations of local anesthetic could lead to permanent neuronal damage.

Anesthesia, Spinal↗