Miguel Yebra

Disseminated-to-Skin Kala-azar and the Acquired Immunodeficiency Syndrome

Excerpt To the editor: The worldwide spread of infection with the human immunodeficiency virus (HIV) may modify the usual expression of regional endemic diseases. Conversely, those atypical forms m...

Hepatic fibrin-ring granulomas: A clinicopathologic study of 23 patients

Twenty-three patients with characteristic hepatic fibrin-ring granulomas were studied. Q fever accounted for 10 cases (43%), visceral leishmaniasis for five cases (22%), boutonneuse fever for two cases (9%), and toxoplasmosis, Hodgkins disease, and allopurinol hypersensitivity for one case each (4%). The etiology remained undetermined in three cases (13%). This report broadens the range of etiologies of hepatic fibrin-ring granulomas to include boutonneuse fever and toxoplasmosis in the differential diagnosis of ring granulomas, and it could serve as a guideline to the clinician and pathologist for the most frequent categories of disease associated with this morphologic pattern.

Drug induction apoptosis assay as predictive value of chemotherapy response in patients with B-cell chronic lymphocytic leukemia

A large number of prognostic factors are available to help predict the course of the disease for patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear the involvement of these well established prognostic factors in the clinical response of the patients with B-CLL to the chemotherapy. The possible association of the patient clinical–biological characteristics and the in vitro response to chemotherapic agents may serve to provide powerful predictive information to identify optimum treatment for patients. An apoptosis induction assay displays the patient in vitro responses to chemotherapy and the possible association with their clinical–biological characteristics. In this study, patients showed a significant better in vitro response to drugs when they were in the initial stages of the disease or with low β2 microglobulin serum level. Response to purine analogues was significantly higher in patients with long lymphocyte doubling time (LDT), few cells expressing CD38, normal karyotype or no p53 deletion, whereas there was no correspondence with ZAP-70 expression. Furthermore, a good correlation was shown between in vitro apoptosis induction assay and the patient clinical response to purine analogues. In conclusion, association between in vitro drug sensitivity and some of the markers considered as prognostic factors could help to develop personalised therapeutic regimens for patients with B-CLL.

Prognostic Factors in Hodgkin's Disease

Hodgkins disease (HD) is a curable tumoral disease. However, there are groups of patients who suffer relapse and the identification of prognostic factors and the adaptation of treatments to individual risk is one the lines of investigation in this disease. A study was performed on 526 patients diagnosed of HD in our hospital between January 1967 and September 2001. An analysis was made of the most important variables in terms of both disease-free and overall survival. Overall survival in this series of patients was 94% at 2 years, 86% at 5 years, 76% at 10 years and 72% at 15 years. Median survival was 249 months. Factors influencing poor prognosis in the overall survival were: male gender (P < 0.0001), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.0001), B symptoms (P < 0.0001), spleen involvement at diagnosis (P = 0.003), no complete remission after first line treatment (P < 0.0001), and more than 30 years-of-age (P < 0.0001). Disease free survival was 83% at 2 years and 68% at 5 years although without reaching the mean follow-up. The disease free survival study revealed the following risk factors: male gender (P = 0.02), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.001), B symptoms (P < 0.001), extranodal or splenic involvement (P < 0.05), and no complete remission after first line treatment (P < 0.0001). The result of treatment optimization is that some factors that were considered to indicate a poor prognosis have disappeared, and that others which are useful have appeared and allow us to establish groups with differing risks of relapse and who could be candidates for differentiated treatments.

Meningeal infiltration by non-myelomatous IgD-secreting plasma cell dyscrasias.

Two cases of meningeal invasion by non-myelomatous plasma cell dyscrasias--a plasma cell leukaemia and an extramedullary plasmacytoma--are described. Both were secretors of IgD paraprotein and both were diagnosed in life, characteristics which we have not found in any other published case of plasma cell leptomeningitis. Analysis of our patients and of another 25 cases suggests as predisposing factors of meningeal invasion the male sex, presentation in the form of plasma cell leukaemia, presence of the IgD paraprotein and tumoral involvement of pleura, lung, pericardium and testicles. Aggressive treatment of this neurological complication controlled the meningeal disorder in some cases. However, the majority died of disseminated disease in spite of systemic chemotherapy. Until an effective treatment can be found, able to maintain remission or cure the systemic disease, prophylaxis of the central nervous system in plasma cell dyscrasias does not appear to be advisable.

Micofenolato de mofetil en el tratamiento de la nefropatía lúpica resistente a ciclofosfamida

1, y en especial lo referido a la glomerulonefritis proliferativa difusa (GNPD), en la que parece establecido el tratamiento con dosis altas de glucocorticoides e inmunodepresores. En este sentido la ciclofosfamida i.v. ha sido considerada como tratamiento de eleccion2; sin embargo, el fallo terapeutico de este farmaco (5-15%), bien descrito sobre todo en pacientes de etnia negra 3 , asi como sus numerosos efectos secundarios, han obligado a buscar otras alternativas. El acido micofenolico, metabolito activo del micofenolato de mofetil (MMF), es un inmunodepresor que inhibe de forma reversible la inosina monofosfato deshidrogenasa, enzima limitante de la sintesis de las purinas, bloqueando selectivamente la proliferacion de linfocitos T y B activados, la formacion de anticuerpos y la glucosilacion de las moleculas de adhesion 4 , involucradas en la etiopatogenia de la nefritis lupica. Describimos nuestra experiencia con MMF en 3 pacientes con lupus eritematoso sistemico (LES) y GNPD refractaria al tratamiento con ciclofosfamida i.v. que fueron biopsiados nuevamente en el curso del tratamiento con MMF. Se trata de un estudio prospectivo de 3 pacientes, un varon y dos mujeres de 28, 40 y 38 anos de edad, respectivamente, que en el momento del diagnostico cumplian criterios de LES. Inicialmente, fueron tratados con ciclofosfamida i.v. 750 mg/m 2

False-positive interpretations in respiratory cytopathology.

We report here the case of a patient diagnosed at first with large-cell carcinoma and treated with chemotherapy. His unusual evolution led to the diagnosis being questioned: he was finally diagnosed with Wegener’s granulomatosis (WG). This is the first description in medical literature of a patient with Wegener’s granulomatosis treated with docetaxel plus irinotecan, with complete long-term remission of his illness attained. We think that this combination could be a therapy option for those cases that are refractory to normal treatment. In addition, this case reminds us of the need to be alert before anomalous tumor behavior, particularly perhaps when making diagnostic assumptions with scarce tumor tissue. The presence of false positives through cytology is well known, though rarely written up in cancer literature.