A case of Werner syndrome with chromosomal abnormality

A 52-year-old woman with diabetes mellitus (DM) complained of weakness of the arms and legs. She was referred to our hospital in November 2002 because of anemia, thyroid tumor and meningioma including DM. She was short in stature, juvenile bilateral cataract, intractable skin ulcers, clavus on the sole of her foot, a bird-like face and high-pitched voice. Typical physical features led to the final diagnosis of Werner's syndrome. Although the myelogram revealed no abnormal findings except erythroid hypoplasia, cytogenetic analysis of bone marrow cells showed deletion of chromosome 20 in 10% of the analyzed cells, which suggested the possibility of that myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) could occur. She had a thyroidectomy because both lobes of the thyroid gland were enlarged and caused hoarseness, In addition, it is common knowledge that the goiter could become malignant. We need to follow her carefully because she might be vulnerable to malignant disease, including leukemia and malignant meningioma.     

Spontaneous and clastogen induced chromosomal breakage in scleroderma.

Spontaneous and clastogen induced chromosomal damage was evaluated in lymphocytes of 10 patients with scleroderma and 21 controls. Peripheral blood lymphocytes from patients with scleroderma not only had elevated rates of spontaneous chromosomal damage (p = 0.002), but also bleomycin induced (p = 0.041), streptonigrin induced (p = 0.035), and 4-nitroquinoline-1-oxide induced (p = 0.032) chromosomal breakage. Our findings suggest that scleroderma lymphocytes may have a generalized susceptibility to DNA damage caused by free radicals.     

T-cell prolymphocytic leukemia with autoimmune manifestations in Nijmegen breakage syndrome

Nijmegen breakage syndrome (NBS) is characterized by growth retardation, microcephaly, mental retardation, immunodeficiency, and predisposition to malignancies, especially B-cell lymphomas. In contrast, leukemia is rare. A 23-year-old NBS patient presented with anemia, thrombocytopenia, and hyperlymphocytosis. The diagnosis of T-cell prolymphocytic leukemia (T-PLL) was confirmed by cytological and immunological assays (TdT(-), CD2(+), CD5(+), CD3m, and CD7(+)). Biological assays also showed a hemolytic anemia and a clotting factor V decrease. The patient was first treated by methylprednisone for 3 weeks. During this period the lymphocyte count decreased. The simultaneous normalization of the hemolysis and of factor V suggested that both could be related to T-PLL. Since T-PLL is refractory to conventional therapies with a poor prognosis, an intensive chemotherapy such as 2'-deoxycoformycin with anti-CDw52 monoclonal antibodies is usually favored. In the present case, however, because of the specific context (i.e., NBS-induced immunodepression, severe hemolytic anemia, and acquired factor V deficiency), he received pentostatin weekly during 1 month and in maintenance during 6 months. At last follow-up (7 months) he showed a persistent control of the lymphocytosis with no side effect.     

Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (Ataxia teleangiectasia or Nijmegen-breakage syndrome): a retrospective survey

Children with chromosomal instability syndromes have an increased risk of developing lymphoma and leukaemia. The treatment of these malignancies is hampered by therapy-associated toxicity and infectious complications. This retrospective analysis evaluated the therapy outcome of 38 children with Ataxia teleangiectasia or Nijmegen-breakage syndrome with acute lymphoblastic leukaemia (ALL, n = 9), Non-Hodgkin lymphoma (NHL, n = 28) and Hodgkin lymphoma (HL, n = 1). All patients with NHL or ALL were treated in accordance to Berlin-Frankfurt-Münster (BFM)- or Co-operative study group for childhood ALL (CoALL)-oriented chemotherapy schedules. 22 patients received significantly reduced-intensity chemotherapy. After a median follow-up of 3·7 years the 10-year overall survival was 58%. Dosage-reduction of chemotherapeutic drugs seemed to have no disadvantages and reduced toxic side effects. On the other hand, reduced-intensity chemotherapy did not prevent second malignancies, which occurred in ten patients with a 10-year incidence of 25%. After individual treatment approaches three of these patients with second malignancies were in complete clinical remission for more than 5 years. We conclude that BFM- or CoALL-oriented chemotherapy is effective and can be administered in children with AT or NBS. Moreover, we show that even second lymphoid malignancies can successfully be treated in these patients.     

Myelodysplasia associated with acquired immunodeficiency syndrome

Two cases of acquired immunodeficiency syndrome with myelodysplasia are presented. Case 1 was admitted because of Pneumocystis carinii pneumonia. Mild anemia, thrombocytopenia and hypersegmented neutrophils were observed. After the administration of trimethoprim-sulfame-thoxazole and antiretroviral therapy, pancytopenia progressed. Bone marrow (BM) showed dysplastic hematopoiesis, suggesting human immunodeficiency virus-myelopathy. Case 2 was hospitalized due to progressive multifocal leukoencephalopathy. BM specimen obtained for thrombocytopenia showed myelodysplasia similar to myelodysplastic syndrome, suggesting that HIV may have an influence on hematopoietic progenitor cells.     

Hyperviscosity syndrome in a patient with acquired immunodeficiency syndrome

The hyperviscosity syndrome is most commonly seen in association with monoclonal gammopathies and has only rarely been described in association with polyclonal hypergammaglobulinemia. We have recently seen a patient with known acquired immunodeficiency syndrome who presented with the hyperviscosity syndrome in the setting of polyclonal hypergammaglobulinemia. To our knowledge, this is the first reported case of a patient with the acquired immunodeficiency syndrome and the hyperviscosity syndrome. The case is presented and the pathogenesis and implications of this diagnosis are discussed.     

A case of acquired immunodeficiency syndrome (AIDS) with histoplasmosis

Fungal infection is a major opportunistic infection in AIDS. Histoplasmosis is often seen in American AIDS, but only one case has been reported in Japan. We report a AIDS case of with histoplasmosis in Japan. The patient was a forty year old male living in the U.S from 1987 to 1990. He was diagnosed as candidial esophagitis in July, 1994, and human immunodeficiency virus type 1 (HIV) antibody positive led to a diagnosis of AIDS. He was admitted to our hospital with fever and lymphadenopathy (neck, abdomen) in August. The therapy for candidial esophagitis was successful and he was recovering, but he was newly diagnosed as atypical mycobacteriosis and Kaposi's sarcoma. Though the fever was slight, it persisted. He was discharged from our hospital in October. He was readmitted for a high fever and dehydration in December, but died after a week from disseminated intravascular coagulation (DIC). Histoplasma capsulatum was found by blood and ascites cultures on second admission. Many yeast like histoplasma cells in granuloma of the liver were found at autopsy. For moderate or severe histoplasmosis, amphotericin B is generally used as the first induction therapy. Fluconazole (FLCZ) is used as a maintenance therapy. We did not use amphotericin B, but used FLCZ because we did not diagnose histoplasmosis before death, and his general condition became worse. The effect of FLCZ therapy was unclear in our case because he had other infections. We expect that AIDS with histoplasimosis will increase in Japan through HIV infected patients infected in the U.S.A.     

Acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome (AIDS) is the lethal end stage of a sexually transmitted disease caused by a virus that is producing the major epidemic of our century. In this article we describe the history and epidemiology of AIDS and the disease states associated with infection with the human immunodeficiency virus (HIV), the apparent cause of AIDS. We review what is known about disease pathogenesis and present an overview of clinical management issues. In the absence of vaccine or therapy to prevent and eradicate this viral infection, we present formative educational approaches for its control.     

Kaposi's sarcoma associated with acquired immunodeficiency syndrome

AIDS-related Kaposi's sarcoma (KS) accounts for 15-20% of cases of AIDS. Clinical presentation is similar to that of classical KS but with an overall more aggressive evolution and cutaneous dissimilation. There is no particular predilection for the lower limbs and frequent lesions are located on the face. Most of the cases have occurred in homosexual males with a moderate immune deficiency (mean CD.4 = 300/mm3). This predilection for gay people has not yet received explanation and the physiopathology of KS is unclear. Treatment of KS with interferon or chemotherapy (Bleomycin) is effective in 30-50% of cases.     

Enteropathy associated with the acquired immunodeficiency syndrome

To explore the effect of the acquired immunodeficiency syndrome on gastrointestinal structure and absorption, the cases of 12 homosexual men with the syndrome and 11 homosexual controls were studied. Seven patients had diarrhea with weight loss. Bacterial or parasitic infections were not detected. All patients were malnourished; had significantly fewer T-lymphocyte helper and suppressor cells; and had significantly lower body weights, midarm circumferences, serum albumin concentrations, and iron binding capacities than homosexual controls. D-Xylose malabsorption and steatorrhea were present in patients, especially those with diarrhea. Jejunal and rectal biopsy samples were histologically abnormal in all patients with diarrhea. Jejunal abnormalities included partial villus atrophy with crypt hyperplasia and increased numbers of intraepithelial lymphocytes. Rectal abnormalities included intranuclear viral inclusions, mast cell infiltration in the lamina propria, and focal cell degeneration near the crypt base. The histologic findings suggest that a specific pathologic process occurs in the lamina propria of the small intestine and colon in some patients with the syndrome.     

Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.     

Tuberculosis in non-Haitian patients with acquired immunodeficiency syndrome

From Jan 1, 1981 to Oct 31, 1984, 24 of 280 (8.6 percent) patients with acquired immunodeficiency syndrome (AIDS) had tuberculosis. No patient with both AIDS and tuberculosis was Haitian. In 15 patients, tuberculosis was diagnosed prior to or concomitant with the diagnosis of AIDS. Twelve patients (50 percent) had Mycobacterium tuberculosis grown from at least one extrapulmonary site. Although the clinical presentation was variable, no patient had cavitary and only one had apical disease. Histologic examination of lung and transbronchial biopsy specimens usually did not reveal acid-fast bacilli or granulomas. Seventeen patients were treated and all showed clinical improvement. Tuberculosis was infrequent but not rare in our patients and often preceded the diagnosis of AIDS. Despite the fact that many of these patients had both severe and extrapulmonary disease, they appeared to respond well to treatment.