Biomedical subjects
Publications and source records attributed to C Nezelof.
Cultured cells from the tumor of a child with bilateral nephroblastoma were studied cytogenetically. All mitoses observed showed the same male karyotype, 46,XY,t(3;17). This translocation constitutes a newly discovered rearrangement that has not been reported previously either in nephroblastoma or in other neoplastic processes.
The histiocytoses represent a heterogeneous group of conditions. Their common denominator is the proliferation and the activation of the mononuclear phagocyte system (MPS). On the basis of recent advances in the knowledge of the distribution, biology, and behavior of the MPS, the following classification is proposed. Reactive and secondary histiocytoses related either to a chronic parasitic intracellular infection or to a patent or latent immunodeficiency state. Some well-established conditions belong to this category--i.e., familial lympho-histiocytosis, cytophagic sinus histiocytosis, Omenn's reticulosis. The dystrophic histiocytoses associated with the storage of either exogenous or endogenous material. It is prudent to separate the storages of homogeneous and chemically defined lipid material (such as cerebroside, sphingomyelin, etc.) from those of heterogeneous lipid material. Proliferative histiocytoses: it is crucial to distinguish the malignant histiocytosis from the histiocytosis X, which seems to be associated with a nonmalignant proliferation of a subpopulation of the MPS, the Langerhans cell system.
Hypercalcemic infantile renal tumors without bone metastases should be considered to be a heterogeneous tumoral entity. Histological and ultrastructural features, different from those of nephroblastoma, should not be exclusively linked with malignant rhabdoid tumors of the kidney. This is reported by the present case, which appears to be a cellular variant of mesoblastic nephroma and was successfully serially transplanted to nude mice. The causes of hypercalcemia in infantile renal tumors are probably related either to NH2-terminal parathormone or to prostaglandin E2 production by the tumoral cells.
On the basis of four cases of patients with persistent lymphadenopathy and at risk for acquired immune deficiency syndrome (AIDS), (3 Haitians, one haemophiliac), histopathologic features of lymph node biopsy in AIDS are recalled. Two main types of alterations of lymph node architecture--follicular hyperplasia or lymphoid depletion--can be associated with interfollicular lesions: vascular proliferation, numerous plasma cells, epithelioid reaction that may reflect an infectious process. Alterations of T-cell subsets distribution were also analyzed using immunocytochemical labelling of frozen sections from lymph nodes. In all four cases, T4 (helper)--lymphocytes were markedly depleted, whereas they normally represent the majority of lymph node T cells. They were replaced by prominent T8 (cytotoxic, suppressor)-cells, particularly inside the follicle. T8 lymphocytes are usually rare in this latter area. The fine analysis of these abnormalities is useful in prodromal or mild forms of AIDS.
We herein report five new cases of severe combined immunodeficiency with hypereosinophilia, the so-called familial reticuloendotheliosis first described by Omenn. It is characterized by erythroderma, polyadenopathy, hepatosplenomegaly, severe and repeated infections, protracted diarrhoea with failure to thrive. There is marked eosinophilia as well as a profound immunodeficiency. The immunologic abnormalities consist of an increase in T cell number, a B cell lymphopenia and a complete lack of humoral and cellular immune responses to antigens. A deficiency of lymphocytes 5'-nucleotidase has been inconstantly found. Histologic findings are characteristic, consisting of severe T and B lymphocyte depletion in lymphoid organs with infiltration by histiocytes and, to a lesser extent, eosinophils. The outcome was uniformly fatal within the first year of life. Treatment by a combination of parenteral nutrition, steroids and epipodophyllotoxin was effective in obtaining the complete remission of clinical manifestations due to the histiocytic and eosinophilic infiltration in two patients. However, the treatment failed to correct the immunologic defect. These results indicate that the histiocytic infiltration is possibly not responsible for the immunologic detect observed in this condition.
Familial erythrophagocytic lymphohistiocytosis, a rare disorder affecting infants, is characterized by a visceral infiltration of histiocytes and lymphocytes resulting in rapid death. It has recently been reported that use of epipodophyllotoxin, VP 16-213, could induce a complete remission of the disease. Such treatment does not, however, prevent fatal CNS relapse. Four patients with the characteristic features of the disease--fever, hepatosplenomegaly, pancytopenia, low plasmatic fibrinogen level, hyperlipidemia, and histiocytic meningitis--are described. These patients were treated with a combination therapy including systemic administration of VP 16-213, steroids, and intrathecal methotrexate followed by cranial irradiation after the age of 12 months. The four patients achieved complete remission of the disease after clearing of the CNS localization. Two patients had secondary relapses, but all four patients have had a disease-free survival exceeding 12 months. All patients have been in remission of the disease for 27, 20, 16, and 13 months, respectively, after disease onset without major setbacks from the treatment. This combination therapy appears to be a promising approach toward long-term remission of the disease.
The case reported concerns a child with chronic intestinal pseudo-obstruction (CIPO) whose digestive manifestations (intestinal adynamia and distension) were present from the age of 6 months and lasted, despite medical and surgical treatments until 4 years of age, when death occurred. The multiple samplings showed important inflammatory reactions centred on the muscular layers of the small intestine, together with degenerative lesions of the muscular fibres, progressively leading to fibrosis and atrophy of the intestinal wall with secondary and final impairment of the myenteric plexuses. The diagnosis of myositis of the small intestine is extremely rare. It is not part of the usual causes of intestinal adynamia and CIPO, which were reviewed. Hollow visceral myopathy and systemic sclerosis of the GI tract were more especially discussed. For lack of etiopathogenic convincing data and of similar observation in the literature, this case may be temporarily considered as an idiopathic myositis of the small intestine, a potentially new cause of CIPO.
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Infantile and childhood lobar pulmonary emphysema (LPE) has finally become a rather straightforward problem after 28 years experience and the important statistics published. Contrary to adult emphysema, and leaving aside the particular aspects of causal lesions, the pediatric form is usually a unilateral lobar or infralobar disorder, and therefore lends itself to surgical treatment.
The histological distribution of A, B, H, Lewis, Pr, i and I blood group antigens (BGA) was studied in 19 nephroblastomas and one mesoblastic nephroma by means of the indirect immunofluorescence technique. In addition to general conclusions about the relatively limited BGA expression in the tumour cells, their histological distribution was found to be related to the differentiation level of these renal embryonic tumours. By comparison with normal embryonic, fetal and adult kidney it was shown that the nephroblastoma differentiation level is not higher than that of a 3-month fetal kidney. Furthermore, i antigen appears to be a non-specific marker of the histiocytic macrophage cells of the nephroblastoma stroma.
Ultrasonic features of liver involvement in six children with chronic granulomatous disease (CGD) are reported. Hepatic granulomas appeared as hypoechoic, poorly marginated areas without posterior enhancement. In two cases, the diagnosis of CGD was suggested by this sonographic pattern. Ultrasound follow-up of the granulomas was used to plan therapy: in three cases, the granulomas subsided with antibiotic treatment alone; three patients underwent surgery because of the persistence of the granuloma and/or its modification into a fluid-filled abscess with good sound transmission throughout. Percutaneous biopsy and aspiration under sonographic guidance were performed in the two cases where CGD had not been diagnosed previously; such procedures permitted recognition of the disease based on histologic study, drainage of a defined abscess, and identification of the infecting organism. Healing of the hepatic lesions was documented in all six patients.
In a 20 year period the authors have seen 8 cases of osteoblastoma in patients less than 15 years old. Four were in the spine, three in the hand and one in the tibia. Three of the four limb osteoblastomas were lost to follow up after curettage, one of them after a recurrence. The fourth one was cured after 9 years. None of the spine lesions recurred after a follow up of from two to 14 years but two of them had a rigid kyphosis. It is concluded that osteoblastoma is normally benign in children. The pathological diagnosis may be difficult. In one the initial diagnosis had been of osteosarcoma. The treatment is based on complete excision. In the spine, it should be accompanied by arthrodesis.
In France, because of routine vaccination, BCG infection is the rule and not the exception. It may thus incidentally reveal a latent immunodeficiency. Eleven cases (10 fatal) of generalized BCG infection observed from 1967 to 1981 at the Hôpital des Enfants-Malades (Paris) are reviewed. The clinico-pathologic analysis of these 11 cases showed that the underlying immunodeficient states were of various natures. They could be grouped under 3 different headings: (1) Cellular immunodeficiency, as part of a severe combined immunodeficiency (5 cases) and Di George's syndrome (1 case); (2) Deficiency in the bactericidal activity of the macrophages, either isolated (2 cases) or associated with fatal granulomatous disease (1 case); (3) unclassified conditions, probably original, associated with chronic Salmonella infection. The heterogeneity of theses cases emphasizes the complexity and diversity of the mechanisms which lead to the elimination of the intracellular agents. Because they provide useful insight into the poorly understood mechanisms of bactericidal activity of macrophages, further investigations of infantile disseminated BCG infection are necessary.
Current ideas about the histiocyte-macrophage system are briefly reviewed and the functions attributed to the system are defined. An anatomico-clinical classification of histiocytic diseases into four categories is suggested: - secondary of associated histiocytosis illustrating, in particular, macrophage function in immune response; - histiocytosis due to dystrophia or overload illustrating mainly phagocyte function and ability to store fats; - Langerhans histiocytosis characterized by the presence of numerous Langerhans cells. - Neoplastic histiocytosis, which is the only genuine malignant tumoral proliferation of the histiocyte-macrophage system.
Bronchiolitis obliterans is an anatomo-clinical entity which may, in young pediatric patients, follow severe viral infections, especially due to measles virus and adenoviruses. After a transient remission, the disease progresses to chronic respiratory failure with dyspneic paroxysms. Diagnosis is based on different investigations which confirm the absence of proximal bronchiolar obstruction and the presence of bronchiolar obliteration. Deficient pulmonary perfusion due to ventilatory defects are demonstrated by pulmonary scintigraphy and even better by digital subtraction pulmonary angiography. Obliteration of non-cartilaginous bronchioli by granulation tissue produces bronchiolar destruction and explains the permenence of alterations. Dissimilarity of the responses of children to acute respiratory viral infection remains unexplained. The degree of the viral load and of the initial immune deficiency as well as the persistence of the virus within the pulmonary tissue probably account for the chronic pulmonary damage.
Autopsy material and clinical information were analyzed in 25 cases of untreated or unsuccessfully treated severe combined immunodeficiency disease and one case successfully treated by bone marrow grafting. Two cases were adenosine deaminase deficient and one was nucleoside phosphorylase deficient. The histological appearance of the thymus fell into four clearly recognizable patterns: simple dysplasia, dysplasia with corticomedullary differentiation, dysplasia with pseudoglandular appearance, and atrophic pattern. Three cases lacked lymph nodes and belonged to the category of thymic dysplasia with pseudoglandular appearance. From the data, the following conclusions can be made: (i) The thymic atrophic pattern is a phase in a dynamic process of which the end result is simple dysplasia or dysplasia with corticomedullary differentiation. (ii) The pseudoglandular pattern represents a disease process of early intrauterine onset. (iii) At least a proportion of the cases represent a T-cell defect rather than a lymphoid stem-cell defect. (iv) The lymphoid germinal centers are not the source of plasma cells. (v) The graft-versus-host reaction probably causes lymphoid cells depletion in lymph nodes and spleen.
Histiocytosis X cells were demonstrated to react with T6 antigen as well as with the M1 and I1 markers of monocytes using immuno-electron microscopy and double labeling immunofluorescence technique. The data confirm the close relationship existing between histiocytic X cells, Langerhans cells and dendritic cells, and suggest to consider the T6 antigen either as an early differentiation marker of thymocytes or as a functional marker of Mononuclear Phagocyte System subpopulations.