Giuseppe Maria Gandolfo

Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia.

The present study is the first to evaluate serum levels of vascular endothelial growth factor (VEGF) in B‐cell chronic lymphocytic leukaemia (CLL). All 68 B‐cell CLL patients and 31 control subjects analysed had detectable serum levels of VEGF, with no statistically significant difference between two proups. An aberrant increase of circulating levels of VEGF was found in only 17.6% of cases. B‐cell CLL patients whose serum VEGF levels were higher than the median (i.e. 194.8 pg/ml) or 75th percentile (i.e. 288.5 pg/ml) values were more frequently at an advanced clinical stage. In contrast, no correlation with other clinico‐biological features representative of either tumour mass [bone marrow (BM) histology, peripheral blood (PB) lymphocytosis, beta‐2 microglobulin (β‐2m), LDH, interleukin‐6 (IL‐6)] or disease‐progression (DP) [lymphocyte doubling time (LDT)] was found.  Serum levels of VEGF predicted the risk of DP in early CLL. Among 41 patients in Binet stage A, progression‐free survival (PFS) was significantly shorter in those patients whose VEGF serum concentrations were above the median value. Interestingly, characteristics of stage A patients stratified according to the median value of VEGF were similar with respect to many clinico‐biological features, thus suggesting a possible independent prognostic role for such a marker. Finally, when added to the Rai subclassification, VEGF serum levels identified two groups with different PFS within stages I–II.  We conclude that increased serum levels of VEGF can be considered useful for predicting the risk of DP and add prognostic information to the Rai subclassification of stage A CLL.

Long‐term follow‐up of autoimmune thrombocytopenic purpura (ATP) patients submitted to splenectomy

Abstract:  We studied the general outcome in 94 adult patients with autoimmune thrombocytopenic purpura (ATP) submitted to splenectomy. Of 84/94 patients who presented a complete or partial response 30 d after splenectomy, 16 (19%) showed one or more relapses. The clinical situation of the 81 patients still under observation is as follows: 13 unrensponsive, 60 completely or partially responsive, without relapses during the follow‐up, 8 completely or partially responsive after one or more relapses. No correlation was found between the favourable splenectomy outcome and age at splenectomy, the diagnosis‐splenectomy interval and initial response to corticosteroids. The probability of disease‐free survival is 83%, projected at 10 yr, while the overall survival is 93%, projected at 10 yr.

Incidence of chromosomes 1 and 17 aneusomy in breast cancer and adjacent tissue: An interphase cytogenetic study

BACKGROUND Characterization of the biopathologic events underlying the early steps of breast carcinogenesis may have a dramatic impact on reducing breast cancer mortality. Genes involved in breast tumorigenesis are localized on chromosomes 1 and 17, and numeric aberrations of these chromosomes have been correlated with breast cancer tumorigenesis and progression. According to the field cancerization hypothesis, specific chromosome aberrations may be present in breast cancer and in normal-appearing adjacent tissue. The latter changes reflect the genomic damage that follows longterm carcinogenic exposure and precede the morphologically detectable neoplastic transformation. We hypothesize that detection of these aberrations in benign breast epithelium may provide a tool for molecular risk assessment. STUDY DESIGN Using fluorescence in situ hybridization with centromere-specific probes, we determined the status of chromosomes 1 and 17 in fresh imprints of 28 samples of primary tumors and 54 samples of their surrounding uninvolved parenchyma taken from patients undergoing operations for breast carcinoma. Ten contralateral breast biopsy specimens collected from patients with previous breast carcinoma were also evaluated as a surrogate of a high-risk group to rule out the hypothesis that chromosomal aneusomy in tumor-adjacent tissue could be related to a paracrine effect of the primary tumor. Ten samples of benign breast tissue taken from patients at low risk were used as controls to define tolerance limits for aneusomy definition. RESULTS Using threshold values of 40% of signal loss and 13% of signal gain to define chromosome aneusomy (ie, mean + 3 SDs of the control group signals), we found the following: 1) almost all primary breast tumors were aneusomic for chromosomes 1 and 17; 2) primary breast tumor and adjacent uninvolved parenchyma shared the same pattern of chromosomes 1 and 17 aneusomy in 66.7% of patients; and 3) chromosomes 1 and 17 aneusomies in contralateral benign breast samples from high-risk patients were not different from those in primary breast tumor or adjacent tissue samples. CONCLUSIONS These results suggest that chromosomes 1 and 17 aneusomy may represent an intermediate biomarker of breast tumorigenesis potentially useful to detect patients at high risk of breast carcinoma who may benefit from preventive interventions.

Danazol Therapy in Refractory Chronic Immune Thrombocytopenic Purpura

We report our experience with danazol in the treatment of patients with refractory immune thrombocytopenic purpura (ITP). The effects of this drug were investigated in 10 patients, 6 males and 4 females, aged from 40 to 85 years, (median 58 years), with a platelet count below 50 X 10(9)/l. The patients had previously been treated with steroids; one of them had also been unsuccessfully splenectomized. Danazol was administered at a dosage of 600 mg/day for 3 months. Before and after treatment, detection of antiplatelet antibodies was performed. Seven patients were treated for 3 months. One of them showed a transient increase of platelet count, in the others, no significant rise was noted. Six patients experienced side effects during treatment. We think that danazol does not appear to be an alternative therapeutical approach in refractory ITP.

Flow cytometric study of lymphocyte subsets in patients at different stages of colorectal carcinoma

PURPOSE: The evaluation of lymphocyte subsets by using monoclonal antibodies in neoplastic patients has provided different results, partly in relation to the stage of the disease. Therefore, as a preliminary study of cancer patients treated with immunomodulating drugs, an analysis of lymphocyte subsets was performed in colorectal carcinoma patients. METHODS: In this study, a flow cytometric evaluation of lymphocyte subsets was performed in 33 patients affected by colorectal carcinoma, with or without metastases. RESULTS: A significant reduction of hemoglobin concentrations and hematocrit was observed in all of these subjects, associated with an evident increase of white blood cells, platelets, and HLA DR-positive T lymphocytes, whereas CD 3-CD 4-positive and CD 20-positive lymphocyte concentrations were decreased. Subjects without metastases showed an evident decrease of hemoglobin concentrations and an increase of white blood cells, platelets and CD 3-HLA DR-positive lymphocytes, while patients with disseminated disease also had reduced mean values of hematocrit, red blood cells, CD 3-CD 4-positive, and CD 20-positive lymphocytes. CONCLUSIONS: The main differences between colorectal carcinoma patients with or without metastases were represented by a decrease of red blood cells, CD 3-CD 4-positive, and CD 20-positive lymphocyte concentrations in the latter group.

Prevalencia de las infecciones de los virus A, B, C y E de la hepatitis en dos grupos de niños de nivel socioeconómico distinto de Santa Cruz, Bolivia

Fundamento y objetivos: Se ha examinado la epidemiologia de las hepatitis A y E, que se transmiten por via gastroenterica, y de las hepatitis B y C, que se transmiten por via parenteral o sexual, en ninos de diferente condicion social residentes en la ciudad de Santa Cruz de la Sierra, Bolivia. Material y metodo: Se selecciono a 1.393 ninos de dos escuelas, una frecuentada por ninos que pertenecen a la mejor clase social de la ciudad (grupo A), y la otra, por ninos de clase social mas pobre (grupo B). Las muestras de sangre fueron obtenidas por medicos de la Universidad de Roma La Sapienza. Los anticuerpos sericos contra los virus de las hepatitis A, B, C y E, y el antigeno de superficie del virus B, se determinaron con metodos inmunoenzimaticos. La significacion se valoro con la prueba de la *2. Resultados: Los anticuerpos contra el virus A estaban presentes en el 82% de los ninos examinados, con una diferencia estadisticamente significativa entre ambos grupos (el 56,3 frente al 94,8%). La prevalencia de los anticuerpos anti-HBc y anti-HBs aumento con la edad, de modo que la infeccion se adquirio prevalentemente en la adolescencia, con una diferencia estadisticamente significativa entre los grupos A y B (el 1,1 frente al 3,8%). El mismo fenomeno se observo en la evaluacion de los anticuerpos anti-VHC (4,7% de positividad solo en el grupo B). Por ultimo, la presencia de anticuerpos contra el virus de la hepatitis E se observo solo en el 1,7% de la poblacion estudiada. Conclusiones: En Bolivia, como en otros paises en vias de desarrollo, las hepatitis viricas representan un grave problema de salud publica. La difusion de la hepatitis virica puede controlarse mejorando las condiciones higienicas y las costumbres de vida. Ademas, un plan de vacunacion contra los virus A y B de la hepatitis es indispensable para la poblacion que vive en un area endemica.

Prevalence of infections by hepatitis A, B, C and E viruses in two different socioeconomic groups of children from Santa Cruz, Bolivia

BACKGROUND AND OBJECTIVES The epidemiology of hepatitis A, E, B and C was analyzed in 1,393 children living in Santa Cruz de la Sierra, Bolivia. They were distributed in two groups according to the social condition. MATERIALS AND METHOD 1,393 children were selected from two different schools: one attended by children belonging to a high social class of the town (group A), and the other school attended by children belonging to the poorest social class (group B). Blood samples were drawn by a team of physicians from Rome University La Sapienza. Serum antibodies against hepatitis A, B, C and E virus, and the hepatitis B surface antigen were evaluated by immunometric methods. The significance was evaluated using the *2 test. RESULTS Antibodies against hepatitis A virus were detected in 82% of examined children, with a significant difference between the two groups (56.3% vs 94.8%). The incidence of anti-HBc antibodies increased with age, so the infection is acquired prevalently in adolescence with a significant difference between both groups (1.1% vs 3.8%). The same phenomenon was observed with anti-HCV antibodies (4.7% positivity only in group B). Serum antibodies against hepatitis E virus were observed in 1.7% cases. CONCLUSIONS In Bolivia, as in other developing countries, viral hepatitis represents a serious burden for public health. Spreading of viral hepatitis can be controlled upon improving hygienic conditions and customs. Moreover, a vaccination plan against hepatitis A and B virus is necessary for the population living in endemic areas.

Hemolytic Anemia and Thrombocytopenia Induced by Cyanidanol

Five patients who received cyanidanol for 4-36 months are presented. Three developed both hemolytic anemia and thrombocytopenia, while 2 had only thrombocytopenia. After suspending the drug the hematological values returned to normal in all of the patients. Drug-dependent platelet antibodies were detected in 4 of the 5 patients and cyanidanol-dependent red blood cell antibodies were present in 3. There are various mechanisms involved in the cyanidanol-induced immune cytopenias and, as in the present study, were sometimes simultaneously observed in the same patient.

Radioiodine-induced changes in lymphocyte subsets in patients with differentiated thyroid carcinoma.

Abstract.This study evaluated changes in lymphocyte subsets in patients with thyroid carcinoma who received iodine-131 for diagnostic and therapeutic purposes. Twenty thyroid cancer patients were entered in the study after total thyroidectomy: ten patients (group A) underwent whole-body scintigraphy with 185 MBq of 131I and the other ten (group B) received 3700 MBq of 131I therapy. All patients were in a hypothyroid state at the time of administration of 131I and started l-thyroxine 150 µg/day 3 days after 131I administration. Free and bound triiodothyronine and thyroxine, thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, thyroid peroxidase/microsomal antibodies, white blood cell, lymphocyte counts and lymphocyte subsets were serially determined at baseline and at days 2, 7, 15, 30 and 60 after 131I administration. Twenty healthy age- and sex-matched individuals were used as a reference population for lymphocyte subset values. In group A only a reduction in NK cells at days 7 (P=0.043) and 15 (P=0.037) was observed. In group B, patients showed a delayed reduction in the total lymphocyte count at days 15, 30 and 60 (P=0.008, 0.004 and 0.018, respectively), and a decrease in B cells throughout the study (at days 7, 15, 30 and 60: P=0.006, 0.0017, 0.0017 and 0.0017 respectively). A transient decrease in NK cells was observed at days 15 (P=0.025) and 30 (P=0.008). Among T cells, the helper phenotype (CD4+) was mainly affected, resulting in a reduction in the CD4+/CD8+ ratio at day 60 (P=0.046). Comparing the two groups, the numbers of B lymphocytes at day 30 (P=0.023) and NK cells at days 2 (P=0.037) and 30 (P=0.023) were significantly lower in group B. Neither group showed any clinical sign of immunosuppression during the follow-up period. In patients with thyroid cancer the sensitivity of lymphocytes to the effects of 131I administered for diagnostic or therapeutic purposes depends upon lymphocyte phenotype and 131I activity. NK cells are the most radiosensitive cells, being reduced even by low 131I activity. At higher activity all subtypes show a reduction, which is more marked and prolonged for B lymphocytes and, to a lesser extent, for T-helper lymphocytes. These changes do not result in clinically relevant immunosuppression.

Borrelia burgdorferi, a great chameleon: know it to recognize it!

Borrelia burgdorferi is a spirochaete that can penetrate the blood–brain barrier in early infection and can cause endothelial damage other than central nervous system lesions. We describe a clinical case of neuroborreliosis that occurred in the absence of classical erythema migrans or arthralgia. Magnetic resonance imaging findings compatible with simil-vasculitis and demyelinating lesions associated with the presence of anti-B. burgdorferi antibodies in the plasma or cerebrospinal liquid is an indication for antimicrobial treatment against B. burgdorferi. An early diagnosis and a prompt establishment of an adequate antibiotic treatment is needed for a successful recovery.