Prospective evaluation of aminopeptidase activities in plasma and peripheral organs of streptozotocin-induced diabetic rats.

The cleavage of peptides by aminopeptidase enzyme types could be among the mechanisms related to certain disruptions on mediator and modulatory functions in diabetes mellitus. In order to examine this hypothesis, we measured representative aminopeptidase activities in tissues of peripheral organs of control and streptozotocin-diabetic rats. None of the examined aminopeptidase activities differed between diabetics and controls in plasma, ileum, stomach or lung. Soluble and membrane-associated alanyl, and membrane-associated cystyl aminopeptidase activities were higher in the kidney of diabetics. Decreased activity was observed in soluble and membrane-associated aspartyl and soluble dipeptidyl-peptidase IV, while increased activity was observed in soluble alanyl, arginyl, and cystyl aminopeptidases in the pancreas of diabetics. In the jejunum, soluble cystyl aminopeptidase increased in diabetics. Soluble arginyl and type-1-pyroglutamyl aminopeptidase and membrane-associated dipeptidyl-peptidase IV activities increased in the liver of diabetics. Membrane-associated dipeptidyl-peptidase IV and alanyl aminopeptidase activities in the spleen were higher in diabetics than in controls. Membrane-associated alanyl aminopeptidase activity also increased in the heart of diabetics. All these changes in streptozotocin-treated rats were avoided by the administration of insulin. Our comparative analysis of a diverse array of aminopeptidase activities supported the proposal that the regulation of peptide cleavage by these enzyme types is associated with the effects of streptozotocin-diabetes mellitus on peripheral organs.

Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression.

BACKGROUND: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. PATIENTS AND METHODS: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. RESULTS: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P < 0.0001). Other variables at relapse with prognostic significance for SFP were age, presence of B symptoms, performance status, bulky disease, number of involved nodal sites, lactate dehydrogenase level, hemoglobin level, histological transformation, the Italian Lymphoma Intergroup prognostic index for FL and the International Prognostic Index for aggressive lymphomas. In the multivariate analysis bulky disease (P=0.01), presence of B symptoms (P=0.03) and FLIPI at relapse (P=0.0003) were the most important variables for predicting SFP. CONCLUSIONS: In patients with FL at first relapse/progression, the FLIPI, along with the presence of bulky disease and B symptoms, are features that predict SFP and thus could be useful to select candidates for experimental treatments.

Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas.

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.

Prognostic features and outcome in patients with diffuse large B-cell lymphoma who do not achieve a complete response to first-line regimens.

BACKGROUND: The current study was conducted to analyze the outcome and prognostic factors of patients with diffuse large B-cell lymphoma (DLCL) who did not achieve a complete response (CR) to first-line treatment. METHODS: The current study was comprised of 83 patients (43 males and 40 females with a median age of 62 years) who did not achieve a CR (58 of whom had primary refractory disease and 25 of whom achieved a partial response) with initial treatment (doxorubicin-containing regimens in 87% of cases) from a series of 239 patients consecutively diagnosed with DLCL at a single institution. Initial variables, response to therapy, and salvage treatment were analyzed to predict survival. RESULTS: Compared with patients who achieved a CR, nonresponders or partial responders more frequently were of advanced age and had a poor performance status (PS), B-symptoms, advanced stage of disease, bone marrow infiltration, increased serum lactate dehydrogenase, and a high-risk International Prognostic Index. Among the 58 patients with primary refractory disease, 18 died during initial treatment due to toxicity (14 patients) or disease progression (4 patients). The main variables predicting early death were a poor PS, age > 60 years, and an immunoblastic DLCL subtype. Twenty-five of these 58 patients were able to receive salvage regimens, with only 1 of them achieving a CR. The median survival for this group of patients was 10 months. With regard to those patients achieving a partial response, 18 of the 25 patients received further therapy with 28% of them achieving a CR. The median survival was 23 months. The degree of the response was found to be the only significant variable with which to predict survival, with 2-year survival rates of 4% and 40%, respectively, for patients with primary refractory disease and patients who achieved a partial response. CONCLUSIONS: The prognosis of patients with primarily refractory DLCL is extremely unfavorable, whereas that of patients who achieve a partial response is slightly better. The inclusion of these patients in experimental trials is limited due to their tendency to be of an older age and to have a poor general status.

¿Arteritis de Takayasu asociada a salmonelosis? / Takayasu's arteritis associated with salmonellosis?

Se trata de una mujer de 18 años con padecimiento actual de dos meses de evolución cracterizado por claudicación de ambos miembros superiores con mayor intensidad del derecho. Con base en la sintomatología, se realizó arteriografía, la cual evidenció estenosis a nivel de la subclavia derecha y fundamantó el diagnóstico de arteritis de Takayasu. En los estudios de laboratorios se encontró reacción de Widal posotiva (tífico O 1:640). La paciente tenía como antecedente el haber padecido fiebre tifoidea hacía tres meses; así lo indicaba la prueba serológica (tífico O 1:320) y la respuesta al tratamiento con ciproxima a dosis convencionales. La paciente también presentó lesiones en miembros inferiores compatibles clínicamente con eritema nodoso. Se ha sugerido una asociación entre varios procesos infecciosos y arteritis de Takayasu. Nosotros presentamos el primer caso de probable asociación entre arteritis de Takayasu e infección por Salmonella tiphy

Prevalence of cytomegalovirus infection in different patient groups of an urban university in Brazil.

This study sought for evidence of previous CMV infection in patients of a general hospital serving the low income population of Rio de Janeiro. An enzyme immunoassay was used to detect anti-CMV antibodies in 713 typical hospital patients classified into eight different groups. Positive tests were found in 87% of pregnant women, 85% of newborns, 61% of pediatric patients, 77% of adolescent patients, 81% of adult patients, 87% of dialysed transplant candidates, 89% of kidney donors, and 92% of patients after transplantation. Depending of the subgroup studied these results carry different meanings and necessitate different clinical approaches. The risk of congenital disease is probably low in view of the reduced number of pregnant women still susceptible to primary infection. The number of primary infections will also be low in transplant recipients. However, those still susceptible will almost certainly acquire the infection from their donor. Prophylactic CMV matching in kidney transplantation is not a realistic approach due to the low probability of finding pairs of seronegative donors and recipients.