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1/60. adult T cell leukemia/lymphoma with lymphopenia in a Korean.

    We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4 T cell (T(H), CD3/CD4 , 57%) and decreased CD8 T cell counts (T(S), CD3/CD8 , 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I dna were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission. ( info)

2/60. Spinocerebellar syndrome in patients infected with human T-lymphotropic virus types I and II (HTLV-I/HTLV-II): report of 3 cases from panama.

    Cerebellar symptoms at onset are unusual in HTLV-I/II-associated tropical spastic paraparesis (TSP). A prospective study of neurological disorders in panama (1985-1990) revealed 13 patients with TSP and 3 with HTLV-I/II-associated spinocerebellar syndrome (HSCS) presenting at onset loss of balance, wide-based stance and gait, truncal instability, and mild leg ataxia (vermian cerebellar syndrome), with absent upper limb dysmetria but with postural tremor, downbeat nystagmus, and dysarthria. In 4-5 years, spinal cord manifestations of TSP developed, including spastic paraparesis, pyramidal signs, bladder and sphincter disturbances. Two patients were infected with HTLV-I and another one, a Guaymi Amerindian woman, with HTLV-II. magnetic resonance imaging (MRI) demonstrated cerebellar atrophy involving predominantly the superior vermis. Mild axonal peripheral neuropathy in the lower limbs, dorsal column involvement and inflammatory myopathy were found by neurophysiology studies. There are 14 similar cases reported in japan and canada, but to our knowledge these are the first documented cases of HSCS in the tropics. A cerebellar syndrome constitutes another form of presentation of HTLV-I/II infection of the nervous system. ( info)

3/60. Acute human T-lymphotropic virus type 1-associated myelopathy: a clinicopathologic study.

    BACKGROUND: Recently, acute human T-lymphotropic virus type 1-associated myelopathy (HAM) was reported clinically without pathologic information. We report an autopsy case of acute HAM. OBJECTIVE: To report the case of a 52-year-old man with acute-onset gait disturbance followed by rapidly progressive paraplegia, who died 9 months later. RESULTS: The postmortem study showed swelling of the thoracic spinal cord. Histologically, there was inflammation and vacuolation in the white matter. CONCLUSION: We propose that these pathologic findings, mimicking tropical spastic paraparesis, may represent the characteristic pathologic features of acute HAM. ( info)

4/60. Detection of human immunodeficiency virus type 2 in brain tissue.

    infection due to human immunodeficiency virus (HIV) type 2 is believed to cause a clinical picture similar to that of hiv-1, although extensive data are not available. In 2 patients with West African exposure and neurologic symptoms, hiv-2 was detected in the central nervous system using dna and rna polymerase chain reaction, in situ hybridization, and immunohistology. In the first patient, the neurologic disease was most likely due to productive infection with hiv-2. In the second, a combination of neuropathologic abnormalities (including the presence of hiv-2) explained the clinical features. Thus hiv-2, like hiv-1, can be readily detected in brain tissue in patients with neurologic abnormalities, although the exact role of hiv-2 in pathogenesis of AIDS-associated neurologic disease requires further study. ( info)

5/60. Increased topical tacrolimus absorption in generalized leukemic erythroderma.

    OBJECTIVE: To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient. CASE SUMMARY: A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained. DISCUSSION: Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma. CONCLUSIONS: tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases. ( info)

6/60. The role of HTLV in hiv-1 neurologic disease.

    We performed a serologic survey for antibodies to HTLV-I/II in the course of a longitudinal study of the neurologic complications of hiv-1 infection. Nine (3.7%) of 242 hiv-1 seropositive subjects and none of 60 hiv-1 seronegative control subjects had antibodies to HTLV-I/II by ELISA. Western blot and polymerase chain reaction confirmed the presence of HTLV-I in 2 subjects and HTLV-II infection in 2 others. Both hiv-1/HTLV-I coinfected subjects and 1 hiv-1/HTLV-II coinfected subject had a slowly progressive myelopathy clinically identical tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). The presence of a myelopathy resembling TSP/HAM in the coinfected subjects suggests that hiv-1 may enhance the expression of neurologic disease caused by HTLV. patients with a progressive myelopathy occurring in association with hiv-1 infection should be serologically tested for the presence of HTLV. Establishing dual infection has therapeutic and prognostic import as 1 of the hiv-1/HTLV-I subjects substantially improved with corticosteroids and the hiv-1/HTLV-II subject with myelopathy had a marked improvement in the absence of therapeutic intervention. ( info)

7/60. HTLV-I and chronic nervous diseases: present status and a look into the future.

    Three entities--multiple sclerosis, tropical spastic paraparesis, and human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM)--may represent manifestations of the same disease, with HTLV-I-like virus playing a role in their etiology. Tests for the presence of antibodies reacting with either HTLV-I-like virions or with p24 (gag) antigen, expression of HTLV-I antigen by cells of peripheral blood lymphocytes or cerebrospinal fluid, and viral sequences detected by in situ hybridization are essential to establish the role of HTLV-I-like virus in the disease. It is not yet known whether an incomplete form of the virus persists in the tissue following initial infection or whether the virus in question shares the gag protein with HTLV-I but carries the envelope of a different virus. It is recommended that investigative units comprising neurologists and laboratory workers be established as soon as possible to pursue vigorously the leads that may throw some light on the etiology of chronic neurological diseases such as multiple sclerosis. ( info)

8/60. Laboratory diagnosis of the first cases of hiv-2 infection in canada.

    Until recently the geographic distribution of infection due to human immunodeficiency virus type 2 (hiv-2) had excluded north america. We report the first two cases of such infection in canada. Both people came from endemic areas of western africa and were asymptomatic. The results of a commercial enzyme immunoassay specific for hiv-1 antibody were positive in both cases, but those of the Western blot technique were indeterminate. The Western blot technique specific for hiv-2 antibody and the indirect fluorescent antibody test were used to verify the presence of hiv-2 antibody. ( info)

9/60. Clinical features of OKT4 /OKT8 adult T-cell leukemia.

    adult T-cell leukemia (ATL) has a range of clinical characteristics. Phenotypically the leukemic cells usually express the helper/inducer associated antigen OKT4 with lack of OKT8. We have observed three patients with acute ATL cytologically indistinguishable from OKT4 /OKT8- ATL but whose neoplastic cells had the unusual phenotype, OKT3 , OKT4 , OKT6-, OKT8 OKT9 /-, OKT11 , Tac /-, TdT-. All patients had abnormal karyotypes and antibodies against anti-ATL associated antigens as well as proviral dna of human T-cell leukemia virus in the leukemic cells. The clinical course was complicated by skin eruptions, hypercalcemia, pulmonary infection and disseminated intravascular coagulopathy. All died of complications shortly after diagnosis. The clinical features of these patients were similar to those of OKT4 /OKT8- ATL. However, their acute course suggests that co-expression surface antigens OKT4 and OKT8 may be a sign of aggressive nature of the disease with poor prognosis. ( info)

10/60. Autocrine growth of interleukin 2-producing leukemic cells in a patient with adult T cell leukemia.

    Leukemic cells in the peripheral blood of a patient with adult T cell leukemia (ATL), which expressed the Tac antigen/interleukin 2 (IL2) receptor, were investigated in vitro for autocrine growth by IL 2. The cells showed spontaneous proliferation in mitogen-free medium. The spontaneous proliferation of the cells was inhibited by monoclonal anti-IL 2 or anti-Tac antibody. These cells were found to produce messenger rna for IL 2 and secrete IL 2 during short-term culture in the same medium. Recombinant IL 2 and IL 2 secreted by the cells enhanced the proliferation of the cells in a dose-dependent manner when added to the initial culture. These findings demonstrate that an autocrine mechanism by IL 2 is involved in the proliferation of ATL cells during short-term culture. ( info)
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