Peripheral neuropathy with distal nerve infiltration revealing a diffuse pleiomorphic malignant lymphoma.
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Biomedical subjects
Publications and source records attributed to M Imbert.
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The myelodysplastic syndromes (MDS) represent a group of syndromes having in common a defective production of one or more myeloid cell lines. They occur in patients which are more than 50 years old without any sex preponderance. The term MDS is replacing the obsolete and archaic term of 'preleukemia' and/or 'oligoblastic leukemia'. The more striking hematologic features are a discrepancy between a cellular bone marrow and a peripheral blood cytopenia. MDS may be idiopathic or secondary. Some of them precede or predispose to the subsequent development of an acute myeloid leukemia. A correct analysis of peripheral blood and bone marrow smears permits to classify MDS and to establish some prognostic features. Some syndromes are easily recognizable such as acquired idiopathic sideroblastic anemia, refractory anemia with excess of blasts, pure refractory cytopenia and acute myelodysplasia with myelofibrosis. Nevertheless this classification does not cover all these syndromes. Some of them with borderline features will be discussed separately. An analysis of a large series of MDS recently published in the literature will be presented as well as nosologic problems which arise. A conceptual effort should be made to recognize and evaluate the MDS.
A computer program to identify normal and pathological blood and marrow cells is presented. It requires an analysis of cellular morphology according to ten simple criteria. These criteria are treated by the Bayesian method; then the program offers, in decreasing order, the cells which are best classified. The responses are analyzed and discussed. This program seems to be well suitable to a computer-assisted teaching (CAT) of cytology. It supplements effectively the traditional methods.
Serum ferritin has been assayed by two methods. Radio-Immunology and Enzymo-Immunology in two group of young females. Iron deficiency is considered as unequivocal if serum ferritin is lower than 20 micrograms/l whatever the method used analysis of red cell indices in iron deficient females has shown that anemia, hypochromia and microcytosis are very late events and that their sensitivity for the diagnosis if iron deficiency is very poor.
In two patients a peripheral neuropathy was the presenting symptom of a noncutaneous peripheral T-cell lymphoma. In the first patient, the neuropathy had a relapsing and remitting course, the symptoms improved under corticosteroid therapy. The second patient suffered from a relentless neuropathy. In both cases the lymphoma infiltrated the peroneal nerve with an angiocentric and perivascular pattern resembling that observed in central nervous system lymphomas. The characterization of T-cell subsets in the lymph node showed cells with the helper/inducer and suppressor/cytotoxic phenotype in the first case and a predominance of cells with the helper/inducer phenotype in the second case. In the nerve, lymphocytes beard the helper/inducer phenotype antigen. A typical paraneoplastic vasculitis of nerve showed clearly different immunologic features.
The amino acid sequence of the protein HMb, a protein of 93 residues (Mr 10757) which represents the major acid-soluble component of the Methanosarcina barkeri nucleoprotein complex, has been established from automated sequence analysis of the protein and from structural data provided by peptides derived from cleavage of the protein at aspartic acid, arginine and methionine residues. The protein HMb is mainly characterized by a high amount of charged residues (15% of acidic residues and 26.8% of basic residues) which are distributed all along the polypeptide chain. The amino acid sequence of the protein HMb is not homologous to any eubacterial, archaebacterial or eukaryotic chromosomal proteins known up to now.
Behavioral tasks were used to investigate how the orbito-insular cortex (OIC) of the cat is involved in complex operations such as the orienting reaction towards a novel stimulus. Six cats were trained preoperatively on a perimetry test to assess their ability to orient the head and eyes to objects presented in restricted regions of the visual field, and on brightness, pattern and form discrimination tasks for food reward in a two-choice discrimination apparatus. Two animals then underwent unilateral chemical lesion of the OIC using injections of ibotenic acid, two others received bilateral lesions of this same area, and the remaining two cats were used as normal controls. Postoperative performance of brightness, pattern and form discrimination was normal following OIC lesions, and no lack of retention was observed. In contrast, the cats with OIC lesions had significant deficits in their visually guided behavior. The cats ignored objects presented in the monocular segment of both sides of the visual field, even after unilateral lesion, and there was an effect on the ability to attend and fixate the central preconditioned stimulus.
Some patients present borderline features between acute myeloid leukemia (AML) and typical myelodysplastic syndromes (MDS): an excess of blasts insufficient to conclusively diagnose AML, yet above the figures usually compatible with MDS or the presence of Auer rods associated with a moderate excess of blasts. This presents considerable difficulties in diagnosis and management. The authors studied 28 such cases using the French-American-British Co-operative Group (FAB) classification, which groups them into a separate category termed "refractory anemia with excess of blasts in transformation" (RAEB-T). This was found to be a heterogenous group. Certain patients (4/28) had a previously established myelodysplasia, but most presented directly as RAEB-T. Two very different pictures emerged: a few patients (4/28) were young, with presentation and evolution similar to classic AML, for whom combination chemotherapy was effective; the majority (20/28) were older, with more varied clinical and cytologic presentation, for whom chemotherapy was of little effect and who presented a picture resembling classic RAEB with a median survival of 10 months.
Fifty-seven patients in initial phase of acute promyelocytic leukemia (APL) were treated in the same department with heparin infusion, platelet transfusions, and two related induction regimens both including cytosine arabinoside and daunorubicin. Clinical and biological findings at presentation were studied. The complete remission (CR) rate was 53%. Twenty-seven patients (47%) died during the initial course of the disease, either before day 5 (early death [ED], n = 7) or after day 5 (death in aplasia [DA], n = 20). Most ED was due to intracerebral hemorrhage (6/7), especially when large hemorrhages had been seen on fundus oculi examination. Most DA was due to multivisceral failure (9/20). No correlation was found between initial disseminated intravascular coagulation (DIC) and death. However, the worsening of coagulation parameters during induction therapy, with or without initial DIC, significantly increased the occurrence of renal and respiratory failure which were particularly frequent during the first month. The median duration of survival was short (3.5 months) and the median duration of CR (11 months) was similar to that of other acute myeloid leukemias treated with the same regimens. The possible causes of the high mortality observed during the initial courses of APL and the possible benefit of a more graduate induction chemotherapy are discussed.
A quantitative re-examination was made of the influence of noradrenergic depletion on the epigenesis of kitten visual cortex. Two methods were used to deplete noradrenaline at the cortical level: stereotaxically controlled injection of 6-hydroxydopamine (6-OHDA) in the coeruleus complex, from which the noradrenergic input to visual cortex arises; intraventricular injection of 6-OHDA. The latter chemical lesion also depleted dopamine levels in the brain. Lesion of the noradrenergic or catecholaminergic systems was performed neonatally or at an age of 3-4 weeks in kittens submitted to five different rearing procedures: normal rearing, dark rearing, monocular rearing, monocular exposure following dark rearing and monocular deprivation following normal rearing. Forty-two kittens between 3 and 12 weeks of age were used for this biochemical and electrophysiological study. Noradrenaline and dopamine levels were measured by a radioenzymatic method in the primary visual cortex of twenty-six kittens. A total of 1263 cells were recorded in area 17 of twenty-six kittens. Combined biochemical and electrophysiological data were obtained in ten 6-OHDA-lesioned kittens. Whatever the mode of chemical lesion used, cortical noradrenergic depletion failed to block either maturation or vision-dependent processes which are known to affect orientation selectivity and/or ocular dominance during the critical period. However, in some cases, the amplitude of the epigenetic functional modifications was slightly reduced in 6-OHDA-treated kittens. The cortical effects of monocular deprivation starting from the age of 5 weeks were studied quantitatively both in lesioned and intact kittens. Disappearance of noradrenaline in area 17 did not prevent the loss of binocularity in cortical cells. However, even when monocular occlusion had been maintained for 2 or 3 weeks in 6-OHDA-treated kittens, ocular dominance shifts were limited to a stage equivalent to that observed in the intact kitten after 5-8 days of monocular occlusion. The amplitude of this partial protective effect was found to be unrelated either to the delay following the chemical lesion, or to the level of noradrenaline remaining in lesioned kitten cortex. Although a putative gating role of noradrenaline cannot be excluded in the development of the intact animal, this report shows that its presence is not required for functional plasticity to occur in kitten area 17.
The development of retinal projections to the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) has been studied in fetal and neonatal mice of the pigmented C57BL/6 strain, using the anterograde transport of tritiated proline and horseradish peroxidase (HRP). Retinal efferents are present contralaterally just beyond the chiasm at E14. By E16 they have grown into both dLGN and SC. Ipsilateral fibers are limited to the proximal optic tract at E16; their growth into dLGN and SC is delayed until E18-birth. During the first 2 postnatal days, an early population of ipsilateral fibers invades the dLGN. Most of these fibers grow in or around the medio-dorsal sector of the dLGN, i.e., the future binocular segment. Fibers are also present, but at lower densities, in the ventral half of the nucleus and thereafter become dispersed or are lost, without at any stage becoming dense. Some denser labeling is also present ipsilaterally in the outer rim of dLGN, just below the optic tract, and later disappears. On the third postnatal day, the ipsilateral fibers establish a deep and denser projection along the medial and dorsal borders of dLGN; this projection overlaps part of the crossed projection, which at this age extends to the whole nucleus. The segregation of each projection starts on the fourth postnatal day, when crossed fibers begin to disappear from the small region of uncrossed projection. This process goes on for another 4 days. During this period, the ipsilateral fibers withdraw from the deepest layer of dLGN, and their terminal density increases gradually; by the eighth postnatal day, both projections are already well separated. Dense crossed projections first appear near the surface of the SC at birth. Prior to this, retinal fibers course throughout neurons of the collicular plate and underneath the pia. The uncrossed fibers invade the SC between birth and P3. They are located preferentially in the anterior and medial aspect of the SC. Subsequently, there occurs a diminution in the laminar and tangential extent of these projections, simultaneously with an intensification of the ipsilateral input to several small, longitudinally oriented clusters located deep to the crossed projections.
Visual response properties were studied in 83 single units recorded in the cat suprageniculate nucleus (Sg). About 70% of the cells were visually driven preferentially by the contralateral eye and triggered by moving stimuli without directional selectivity. Receptive fields were usually of a large size (greater than 20 degrees) and for half the cells, extended into both contralateral and ipsilateral fields of vision. No retinotopy nor functional clustering within the nucleus could be demonstrated. These properties of the visual neurons in the Sg nucleus are discussed in relation to the afferent and efferent connections of this nucleus.
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The orbital region of the cortex in the cat is known to be involved in multimodal sensory functions. Visual afferent connections of this area have been investigated using the horseradish peroxidase technique. Our results demonstrate the existence of projections from ipsilateral thalamic nuclei essentially at the suprageniculate and magnocellular medial geniculate junction, well known to have multimodal physiological properties.
In 164 patients with Hodgkin's disease staged between 1973 and 1979 the response to the 3 initial cycles of multiagent chemotherapy was evaluated as a prognosticator of survival. Treatment of localized disease (Stages I, II, III1) consisted of 3 cycles of chemotherapy followed by subtotal nodal irradiation, including the splenic area in non splenectomized patients. Treatment of extended disease (Stage III2 and IV) consisted of 6 cycles followed by low-dosage radiotherapy of initial bulky disease. Five-year actuarial survival was 88% in Stage I, 80% in II, 100% in III1, 45% in III2 and IV. Chemotherapy-induced complete remission after 3 cycles (CH leads to CR) was associated with a favorable prognosis. Five-year survival of Stage III2 and IV patients was better in those who reached CH leads to CR than in those who did not (75% versus 25%; P less than 0.01). This relationship between CH leads to CR and five-year survival was confirmed in patients with localized disease, as shown in Stage II patients (respectively 97% versus 63%; P less than 0.05). Therefore the response to initial chemotherapy provides a new prognostic factor that may serve to delineate a "high-risk" group of patients. The latter deserve aggressive therapy while those in the favorable group would benefit from a less aggressive combined regimen that would minimize long-term complications.
A physiological and anatomical study of the dorsal lateral geniculate nucleus (dlGn) in pigmented C57BL/6 Mice is reported. Neurons responding to the ipsilateral eye are clustered in a region near the medial border of dlGn, and are surrounded by contralateral neurons. Electrode penetrations in this part of dlGn show the existence of contra/ipsi/contralateral projection lines. Practically only the contralateral field of vision is represented in each dlGn. Local HRP injections show evidence in the retina of a decussation line for contralateral retinogeniculate projections, the border of which follows the inner border of the region of ipsilateral projection. The mean diameter of ipsilateral retinogeniculate ganglion cells is larger than that of contralateral cells.
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The haematological features of 118 cases of primary myelodysplastic syndromes (PMDS) were reviewed to see how these could be related and classified according to the recent FAB proposals. A majority of the cases were elderly who presented with a macrocytic or normocytic anaemia and reticulocytopenia. Cases of acquired idiopathic sideroblastic anaemia (AISA) usually had normal leucocyte and platelet counts, erythroid hyperplasia, marked dyserythropoiesis and more than 20% ringed sideroblasts. Cases of refractory anaemia with excess of blasts (RAEB) had frequent neutropenia and thrombopenia usually with prominent dysgranulopoiesis and dysthrombopoiesis. Refractory anaemia or refractory cytopenia appeared morphologically to be a heterogeneous group. Leukaemic transformation did not occur in any of these 16 cases of AISA whereas six of the 34 cases of RAEB transformed into acute leukaemia. It appears that the cases of PMDS present with well defined haematological features which permit recognition of different groups; these latter groups appear to be morphologically and prognostically distinct.