Cyclosporine-induced lymphoma following a unilateral lung transplant. The Toronto Lung Transplant Group

Lymphomas are a well-known complication of therapy following organ transplantation. To date we have seen one lymphoma develop in a group of 24 patients who have undergone single or double lung transplantation. We report a 16-year-old man who developed multiple, rapidly appearing pulmonary nodules four months following transplantation. The Epstein-Barr virus and immunosuppressant drugs such as cyclosporine A have been implicated in the pathogenesis of this patient's rapidly progressive and fatal course.     

Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: Lessons from human and nonhuman primate studies

Here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (HIV) in the central nervous system (CNS): (1) HIV infection in the CNS is a compartmentalized infection, with the virus-infected macrophages entering the CNS early, infecting resident microglia and astrocytes, and achieving a state of latency with evolution toward a fulminant CNS infection late in the course of disease; or alternatively, (2) events in the periphery lead to altered monocyte/macrophage (MΦ) homeostasis, with increased CNS invasion of infected and/or uninfected MΦs. Here the authors have reevaluated evidence presented in the favor of the latter model, with a discussion of phenotypic characteristics distinguishing normal resident microglia with those accumulating in HIV encephalitis (HIVE). CD163 is normally expressed by perivascular MΦs but not resident microglia in normal CNS of humans and rhesus macaques. In agreement with other studies, the authors demonstrate expression of CD163 by brain MΦs in HIVE and simian immunodeficiency virus encephalitis (SIVE). CNS tissues from HIV-sero positive individuals with HIVE or HIV-associated progressive multifocal leukoencephalopathy (PML) were also examined. In HIVE, the authors further demonstrate colocalization of CD163 and CD16 (FcγIII recptor) gene expression, the latter marker associated with HIV infection of monocyte in vivo and permissivity of infection. Indeed, CD163⁺ MΦs and microglia are often productively infected in HIVE CNS. In SIV infected rhesus macaques, CD163⁺ cells accumulate perivascularly, within nodular lesions and the parenchyma in animals with encephalitis. Likewise, parenchymal microglia and perivascular MΦs are CD163⁺ in HIVE. In contrast to HIVE, CD163⁺ perivascular and parenchymal MΦs in HIV-associated PML were only associated with areas of demyelinating lesions. Interestingly, SIV-infected rhesus macaques whose viral burden was predominantly at 1 × 10⁶ copies/ml or greater developed encephalitis. To further investigate the relationship between CD163⁺/CD16⁺ MΦs/microglia in the CNS and altered homeostasis in the periphery, the authors performed flow-cytometric analyses of peripheral blood mononuclear cells (PBMCs) from SIV-infected rhesus macaques. The results demonstrate an increase in the percent frequency of CD163⁺/CD16⁺ monocytes in animals with detectable virus that correlated significantly with increased viral burden and CD4⁺ T-cell decline. These results suggest the importance of this monocyte subset in HIV/SIV CNS disease, and also in the immune pathogenesis of lentiviral infection. The authors further discuss the potential role of CD163⁺/CD16⁺ monocyte/MΦ subset expansion, altered myeloid homeostasis, and potential consequences for immune polarization and suppression. The results and discussion here suggest new avenues for the development of acquired immunodeficiency syndrome (AIDS) therapeutics and vaccine design.     

Gonadal function after cancer treatments in childhood

Treatments given for childhood malignancies can alter gonadal function by several mechanisms: (1) cranial irradiation may cause either gonadotrophin deficiency or premature puberty. (2) Irradiation of the testes can induce germinal epithelium dysfunction even if the dose delivered is very low; Leydig cell failure occurs beyond 5-6 Gy and ovarian insufficiency beyond 6-7 Gy. (3) Chemotherapy is considerably more toxic for the germinal epithelium of the testes than for the ovaries; alkylating agents are especially toxic. Analysis of the consequences of preparation for bone marrow transplantation by chemotherapy or total body irradiation will be required when longer follow-up are available.     

Growth and endocrine disorders in optic glioma

Hypothalamo-pituitary function in children with optic glioma may be impaired by the tumour itself and by the high cranial radiation doses used in treatment. This study evaluates the effect of optic glioma and its treatment on patient growth and pubertal development. Twenty-one patients (13 boys, 8 girls), treated for optic glioma by cranial irradiation (45–55 Grays) at a mean age of 5.4 years, were evaluated before (n=10) and/or after (n=21) irradiation. Growth hormone (GH) deficiency was present in only 1 patient tested before irradiation and in all patients after irradiation. Precocious puberty occurred in 7/21 cases, before irradiation in 5 patients and after irradiation in 2 patients. The cumulative height loss during the 2 years after irradiation was 0.2±0.2 SD (m±SEM) in 7 patients with precocious puberty and 1.1±0.2 SD in 14 prepubertal patients (P<0.01). The corresponding bone age advance over chronological age, evaluated 1–3 years after irradiation, was 1.1±0.5 and –0.7±0.3 year in the two groups (P<0.01). The mean height loss between time of irradiation and the final height was 2.3±0.6 SD (n=6). Primary amenorrhoea, associated with low oestradiol levels, occurred in two of the three girls of pubertal age. These data indicate that the high dose of cranial radiation used to treat optic glioma invariably results in GH deficiency within 2 years and that hGH therapy is required when GH deficiency is documented. Precocious puberty, resulting in apparently normal growth velocity in spite of GH deficiency, should be treated with luteinizing hormone-releasing hormone analogues because of the risk of accelerated bone maturation and reduced final height.     

Statural growth following irradiation of the central nervous system for medulloblastoma of the posterior fossa. Retrospective analysis of 45 cases

Treatment of medulloblastoma in children with head and spinal irradiation causes growth hormone deficiency and growth retardation. The present study deals with 45 patients presenting a follow-up time superior to 4 years; some of them having reached their final height. The mean final height is 3 standard deviations below normal mean. Growth retardation which occurred in 42 of 45 children, appears to be due to two major factors: 1) GH deficiency in 42 cases as assessed by the arginine insulin tolerance test. 2) Spinal lesions due to irradiation, causing early growth retardation and a reduced trunk length in most of these children. The response to hGH treatment (10 mg/kg/yr) was not sufficient in this group of patients.     

Cushing's syndrome caused by multinodular adrenocortical dysplasia in a 3-year-old child. Association with a neurologic syndrome

A case of multinodular pigmented adrenocortical hyperplasia occurring in a child aged 4 years is reported. The disease suggested an autonomously functioning lesion with low plasma ACTH. At surgery both adrenals presented with brown or yellow patches on the surface corresponding to multiple nodules. Unilateral adrenalectomy was followed by complete recovery and normal ACTH response to IV lysine vasopressin with a follow-up of 3 years. The patient also presented mild spastic diplegia and retarded mental development of unexplained origin.     

Chemotherapy and ovarian function. Retrospective analysis in 17 girls treated for malignant tumor or hematologic disease

Ovarian function was investigated in 17 patients aged 13 5/12 to 30 years who had received various types of combined chemotherapy without any irradiation. Ovarian insufficiency was found in 6 cases with amenorrhea (n = 5) or irregular menstruations (n = 1). There is a high risk of sterility in these cases although as described in one case, a normal pregnancy occurred in spite of evidence of ovarian failure. Cyclophosphamide seemed to be less harmful when given before puberty. Great variations in individual susceptibility for relatively low doses were observed with this drug. The combination with other drugs in some protocols might play a role in these cases. At variance with results reported in adults, the MOPP chemotherapy used in children with Hodgkin's disease did not induce ovarian dysfunction.     

Correlation between maternal and fetal immunoglobulin E levels

Immunoglobulin E (IgE) concentrations were measured in 157 paired samples of maternal-fetal sera. A correlation was found between maternal and fetal IgE levels, in contrast to earlier reports dealing with smaller series. The correlation is probably not due to placental transfer of maternal IgE but rather to genetic factors. The possible role of IgE in the fetal immune response is discussed.     

Effect of hematologic treatment on the growth and puberty of children with thalassemia major

This study reports on the endocrine abnormalities associated with delayed growth and puberty, observed in 10 children presenting with thalassemia major. Hormonal changes were followed up during treatment with regular transfusions and efficient chelating agents. Recovery of growth and onset of puberty were observed in most cases. When puberty was delayed, an associated substitutive treatment with sexual hormones was useful. In one case only, an isolated gonadotropic deficiency could be proven. In all cases STH, TSH and PRL secretions were normal. Without efficient and early treatment, the main consequence of the disease with respects to growth seems to be the risk of delayed puberty, mainly functional, or rarely hypogonadotropic due to definite LH and FSH deficiency.