Necrosis avascular de cabeza y cuello de fémur en un paciente con sida / Avascular osteonecrosis of femoral head and neck in an AIDS patient

Avascular osteonecrosis (AON) has increased in the last few years in patients infected with the human immunodeficiency virus type-1 (HIV-1). The most commonly affected bone is the femoral head and neck. Frequently these bilateral and clinical findings include moderate to severe pain and functional impotence of the affected joints. The etiology is multifactorial and highly active antiretroviral therapy (HAART) with protease inhibitors (PI) is probably related to its development. In the evolution, a total hip replacement may be needed. We present an hemophilic patient with AIDS, who developed a bilateral AON of the femoral head and neck during HAART.

La osteonecrosis avascular (ONA) es una complicación que se describe con frecuencia creciente en pacientes infectados por el virus de la inmunodeficiencia humana tipo-1 (HIV-1). En su localización más común compromete la cabeza y cuello del fémur con dolor e impotencia funcional, en una o ambas caderas. Su etiología es multifactorial y la terapia antirretroviral de alta eficacia (HAART) con inhibidoresde proteasa (IP) puede estar relacionada con la patogenia. En su evolución puede requerir el reemplazo total de la cadera con la colocación de una prótesis. Se presenta un paciente hemofílico, HIV-1 seropositivo, quedesarrolló una ONA bilateral de cabeza y cuello de fémur mientras se encontraba bajo HAART.

Monocyte differentiation and HIV replication after prolonged culture of peripheral blood mononuclear cells from HIV-infected individuals.

Primary cultures of peripheral blood mononuclear cells (PBMC) from 51 HIV+ hemophiliac patients (HIV+ PBMC) were set up, allowing undisturbed cellular interaction in the absence of any exogenous stimuli. The optimum time for p24 detection was between 12 and 25 days. Infective virus was recovered from the culture supernatants (HIV+ SN) and the amount of p24 released ranged from 25 to 5300 pg/ml. Cells of the monocyte/macrophage (M/M) lineage were the main source of HIV in the HIV+ SN, as judged by intracellular staining of permeabilized cells with anti-p24 (KC57 monoclonal antibody) and flow cytometry analysis. M/M activation, differentiation, and proliferation occurred along the culture before the peak of in vitro HIV replication. Release of HIV p24 was highest in patients with >200 CD4+ T lymphocytes/mm3 who did not receive highly active antiretroviral therapy (HAART), but it was still detectable in 60-90% of patients who had responded to 1-2 years of HAART, reducing their plasma viral load to undetectable levels. It is proposed that this simple experimental system can be used to assess ongoing HIV infection of M/M with the patient's own viral variants.

[Cavum lymphoma in a hemophilic patient with AIDS]. / Linfoma de cavum en un paciente hemofílico con SIDA.

Intermediate and highly malignant non-Hodgkin and primary central nervous system lymphomas are marker diseases for AIDS. Cavum and oropharynx involvement by these tumors is uncommon. Although there are few cases reported in the literature, these may be primary localizations of the tumor. We present a hemophilic HIV+ patient with non-Hodgkin lymphoma of the cavum. The histologic diagnosis was high-grade, pleomorphic, centroblastic lymphoma. The patient was treated with chemotherapy plus intrathecal chemotherapy and highly active antiretroviral therapy (HAART). His evolution has been excellent. One year after diagnosis, the patient is asymptomatic with no evidence of residual tumor, and responding well to HAART.

[The future of oncohematology]. / El futuro de la oncohematología.

The last 40 years have witnessed important changes in the understanding and treatment of oncohematological affections. Palliative therapy was gradually replaced by chemotherapy (CT) which rapidly proved unexpectedly effective. In 1948, the first antifolic drugs, aminopterin and methotrexate, were discovered, followed in 1950 by the corticoids and in 1953 by antipurine agents. By 1967, a combination of these drugs yielded a survival index of 50% in acute lymphoblastic leukemia (ALL) with a progressive increase in all important cancer centers today, including in GATLA (Argentine Group for Acute Leukemia). As for acute myeloblastic leukemia (AML) the CT results were not as spectacular although now there is a 25% survival index which reaches 40-50% in young adults. As for allogeneic transplant in acute leukemia, its use must be evaluated for each patient and for each circumstance. Leukemias are genetic diseases for which gene therapy undoubtedly has potential value. However, the problems raised by the election of the right gene or gene marker and specially of the adequate vector have not yet been solved. In Hodgkin's disease, the results obtained with CT since the decade of the 60s have been spectacular and today different combinations of drugs have yielded a survival rate above 80%. Immunotherapy with or without CT has opened up a completely new and promising field. The route from basic research to clinical application has been long and arduous but the results obtained in leukemia and lymphomas have undoubtedly been life-saving and hopefully will open up even better possibilities in the near future.

Extensor supracondylar femoral osteotomy as treatment for flexed haemophilic knee.

The experience with extensor supracondylar femoral osteotomy as treatment for the flexed haemophilic knee is presented with the description of 19 patients treated during a 30-year period (1968-98). The average age of the patients was 16 (8-35 years), and the average age follow-up was 13 years (3-30 years). Six patients had flexion fixed deformity while the rest presented 40 degrees average range of motion (10-75 degrees). In 13 patients a single osteotomy without internal fixation was performed, in one an osteosynthesis with a condylar plate and in five stabilization was achieved by means of Blount staples. Previous surgery was performed in two patients with patello-femoral ankylosis. The osteotomy site was consolidated in every patient and the deformity was corrected. Two bleeding complications were observed: one haemarthrosis and one psoas haematoma. Flexion relapsed in one patient who underwent another procedure after 12 years. One patient presented with a peroneal nerve paralysis; another one a genu recurvartum; which required flexor osteotomy. The extensor supracondylar femoral osteotomy is a procedure that aligns the limb with scarce modification of articular mobility.

[Concurrence of cytochemical and immune patterns of different cell lines in cases of acute leukemia]. / Concurrencia de marcación citoquímica e inmune de diferentes linajes celulares en casos de leucemias agudas.

Mixed, bilineal, biclonal and hybrid leukemias are synonymous, differing from biphenotypical ones. Mixed acute leukemia is defined by the coincidence of 1) two cytochemical markers of different lineage, or 2) one of them with more than one opposite immunological marker, or 3) more than one immunological marker opposite to another immunological lineage. Seven cases of mixed acute leukemia are presented, two of which showed posttreatment switching. It is concluded that mixed acute leukemias are associated with a poor prognosis, and therapeutic criteria are defined.

Suppression of T cell proliferation induced by concanavalin A in hemophilia patients

Se valoró la función supresora inducida por Concanavalina A (Con A) en 48 pacientes con hemofilia severa. Cuando se adicionaron cantidades variavles de células inducidas por Con A a un número constante de células T autólogas estimuladas por PHA, se pudieron diferenciar dos grupos de pacientes: en el grupo A (60%) así como en los controles normales, los valores de supresión obtenidos fueron superiores al agregar mayor número de células inducidas por Con A; en el grupo B el agregado en cantidades crecientes de células inducidas por Con A no produjo supresión de la proliferación de células T estimuladas con PHA. El efecto observado en el grupo B pudo ser corregido con inhibidores del metabolismo exidativo del ácido araquidónico presentes durante la etapa de inducción. Los perfiles de supresión definidos no guardaron correlación con la serología para HIV-1 o HBV. Al valorar la evolución clínica, teniendo en cuenta los síntomas y signos del complejo relacionado al SIDA, ésta tendió a ser mejor en el grupo B de pacientes. Se sugiere que la disminución de la actividad supresora inducida por Con A observada en el grupo B es el resultado de un proceso regulatorio normal que involucra productos del metabolismo oxidativo del ácido araquidónico

An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.

A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma.

In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.