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Biomedical subjects

G Specchia

Publications and source records attributed to G Specchia.

At least 55 records · Page 3Linked to original sources
PubMed1999

Therapy of molecular relapse in acute promyelocytic leukemia.

Fourteen patients with PML/RARalpha-positive acute promyelocytic leukemia (APL) were given salvage therapy at the time of first molecular relapse. All patients had achieved first molecular remission after the AIDA protocol (all-trans retinoic acid [ATRA] + idarubicin) and were being prospectively monitored by reverse transcriptase-polymerase chain reaction (RT-PCR). Molecular relapse was defined as reappearance of RT-PCR-positivity for the PML/RARalpha fusion (sensitivity 10(-4)) in 2 successive marrow samples collected during postconsolidation monitoring. The median duration of first molecular remission was 7.5 months (range, 2 to 25). Salvage therapy consisted of oral ATRA for 30 days followed by 4 daily courses of chemotherapy (CHT) with cytarabine 1 g/m(2)/d and mitoxantrone 6 mg/m(2)/d. Second molecular remission was obtained in 12 of 14 patients (86%). Seven of these 12 attained molecular remission after ATRA alone. Of the 2 patients who persisted PCR(+) after CHT, 1 died in remission and 1 progressed to hematologic relapse. Of 12 patients PCR(-), 8 received consolidation with autologous bone marrow transplantation (ABMT), and 4 received ATRA-containing maintenance. Ten patients in this group are in sustained second molecular remission at a median time of 9.5+ months (range, 4 to 22+) and 2 underwent hematologic relapse 6 and 13 months, respectively, after transient second molecular remission. The 2-year Kaplan and Meier survival estimate from time of relapse was 92% (95% confidence interval [CI]: 61% to 98%) in this series, and 44% (95% CI: 35% to 52%) in a previous series of 37 patients who received the same treatment at the time of hematologic recurrence (P <.05, by log-rank test). This study suggests that early administration of salvage therapy is advantageous in APL and represents the first experience on therapy of molecular relapse in acute leukemia.

Adult↗
PubMed1999

From plaque biology to clinical setting.

Coronary atherosclerosis may cause acute and chronic ischemic syndromes; the former are caused by "acute plaque events," mostly thrombosis complicating vulnerable ruptured plaques, namely severe lesions with large core, thin cap, and weak shoulder infiltrated by activated inflammatory cells. Plaque rupture may also occur in nonischemic settings and is not obligatorily complicated by thrombosis. Furthermore, plaque rupture is not the only thrombus substrate in acute ischemic syndromes: Superficial erosion of fibrous plaques is found in 44% of acute thrombi in sudden coronary deaths and in 25% of those in acute myocardial infarctions. Coronary thrombosis appears to be triggered by superficial intimal inflammation in plaque ulceration and by neointimal hyperplasia in plaque erosion. "Endogenous" and, recently, exogenous factors, particularly infective intracellular organisms, have been proposed as major contributors to plaque inflammation, activation, and vulnerability. Possible exogenous triggers are DNA and RNA viruses and intracellular bacteria such as Chlamydia pneumoniae, which has been identified with microbiological, ultrastructural, immunohistochemical, and molecular tools in a consistent proportion of human plaque samples. Chlamydia increases local thrombogenicity and is associated with an atherogenic lipid profile. Systemic indexes of inflammation, such as PCR, SAA, and fibrinogen, are also increased in acute syndromes and common infectious diseases with high morbidity and minimal clinical impact are good candidates; Helicobacter pylori is a major one. Infectious agents could link local and systemic inflammation: White cells infected in its target tissue could circulate into the flow and be captured, on a specific local trigger, into vessel walls thus stimulating local inflammation.

Chlamydia Infections↗
PubMed1999

Plasma levels of interleukin 2, 6, 10 and phenotypic characterization of circulating T lymphocytes in ischemic heart disease.

The purpose of this study was to assess lymphocyte receptors expression in patients with ischemic heart diseases, as well as to measure the plasma levels of interleukin (IL) 2, 6 and 10. T Lymphocytes are found in large numbers in human atherosclerotic plaques, indicating that immune and inflammatory mechanisms are important factors in the pathogenesis of atherosclerosis. Recent data have also implicated T lymphocytes in the pathogenetic mechanism of unstable angina and ischemic heart disease. Three groups of patients were studied: 42 with an acute ischemic syndrome (AIS), 36 with stable angina (SA) and 39 healthy controls. To characterize lymphocyte phenotype, flow cytometry was performed in whole-blood samples. IL-2, IL-6 and IL-10 were measured using the ELISA method. Double fluorescence evaluation showed an increase in CD8+/CD11b+ cells (cytotoxic T lymphocytes) and in CD11b+/CD16+CD56+ cells (NK lymphocytes) in the AIS group and in SA group as compared to the control group (P < 0.05 and P < 0.001, respectively). IL-2 was increased in the AIS and SA groups compared to the control group (AIS 4.5 +/- 0.5 pg/ml; SA 6.3 +/- 0.6 pg/ml; controls 2.4 +/- 0.8 pg/ml, P < 0.05), whereas IL-6 was higher in the AIS group than in the other two groups (AIS 10.8 +/- 1.8 pg/ml; SA 1.8 +/- 0.8 pg/ml; controls 1.2 +/- 0.6 pg/ml, P < 0.0001). These data show that patients with ischemic heart disease have an increase in circulating cytotoxic T lymphocytes and in IL-2 plasma levels, irrespective of their clinical presentation, compared to normal control subjects, whereas IL-6 is elevated only in patients with AIS.

Angina Pectoris↗
PubMed1999

Liquid chromatographic determination of urinary 5-methyl-2'-deoxycytidine and pseudouridine as potential biological markers for leukaemia.

A simple reversed-phase liquid chromatographic (LC) method for the determination of urinary 5-methyl-2'-deoxycytidine (m5dCyd), recently claimed (on the basis of an imuno-technique) to be a potential marker for leukaemia, has been developed. Sample pre-treatment is based on a microcolumn clean-up step with an average recovery of 79% and a RSD of 3%. Detection limit was 0.2 microg/ml which is about tenfold lower than levels previously measured by an ELISA method in urine of healthy individuals. The creatinine (Cre) excretion, necessary for normalising the m5dCyd excretion, was evaluated by ion-pair liquid chromatography which permitted the simultaneous determination of pseudouridine (psi), a modified nucleoside also potentially useful as a marker for leukaemia. The described LC procedures were applied to the analysis of urine samples from healthy individuals and leukaemia patients. While the urinary psi/Cre ratio was found significantly increased for leukaemia patients, the urinary m5dCyd levels in healthy individuals were below the detection limits and did not increase in presence of the malignant disease.

Acute Disease↗
PubMed1999

Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche dell' Adulto.

To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections, a randomized, placebo-controlled, double-blind, multicenter trial was conducted: 405 neutropenic patients with hematologic malignancies were randomly assigned to receive either itraconazole, 2.5 mg/kg every 12 hours (201 patients), or placebo (204 patients). Proven and suspected deep fungal infection occurred in 24% of itraconazole recipients and in 33% of placebo recipients, a difference of 9 percentage points (95% confidence interval [CI], 0.6% to 22.5%; P = .035). Fungemia due to Candida species was documented in 0.5% of itraconazole recipients and in 4% of placebo recipients, a difference of 3.5 percentage points (95% CI, 0.5% to 6%; P = .01). Deaths due to candidemia occurred in none of the itraconazole recipients compared with 4 placebo recipients, a difference of 2 percentage points (95% CI, 0.05% to 4%; P = .06). Aspergillus infection was documented in four itraconazole recipients (one death) and one placebo recipient (one death). Side effects causing drug interruption occurred in 18% of itraconazole recipients and 13% of placebo recipients. Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to Candida species.

Administration, Oral↗
PubMed1999

Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction.

OBJECTIVE: To evaluate the prevalence of plaque erosion as a substrate for coronary thrombosis. DESIGN: Pathological study in patients with acute myocardial infarction not treated with thrombolysis or coronary interventional procedures. PATIENTS: 298 consecutive patients (189 men, mean (SD) age 66 (11) years; 109 women, 74 (8) years) dying in hospital between 1984 and 1996 from acute myocardial infarction, diagnosed by ECG changes and rise in cardiac enzymes. MAIN OUTCOME MEASURES: Histopathological determination of plaque erosion as substrate for acute thrombosis; location and histological type of coronary thrombosis; acute and healed myocardial infarcts; ventricular rupture. RESULTS: Acute coronary thrombi were found in 291 hearts (98%); in 74 cases (25%; 40/107 women (37.4%) and 34/184 men (18.5%); p = 0.0004), the plaque substrate for thrombosis was erosion. Healed infarcts were found in 37.5% of men v 22% of women (p = 0.01). Heart rupture was more common in women than in men (22% v 10.5%, p = 0.01). The distribution of infarcts, thrombus location, heart rupture, and healed infarcts was similar in cases of plaque rupture and plaque erosion. CONCLUSIONS: Plaque erosion is an important substrate for coronary thrombosis in patients dying of acute myocardial infarction. Its prevalence is significantly higher in women than in men.

Aged↗
PubMed1999

Evaluation of trisomy 12 by fluorescence in situ hybridization in peripheral blood, bone marrow and lymph nodes of patients with B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVE: Trisomy 12 is the most common numerical chromosomal aberration in patients with B-cell chronic lymphocytic leukemia (B-CLL). Fluorescence in situ hybridization (FISH) has improved the detection of this cytogenetic abnormality and has made detection possible in all phases of the cell cycle. The presence of the trisomy 12 positive (+12) cell population has generally been investigated in leukemic cells obtained from the peripheral blood of CLL patients. To ascertain whether trisomy 12 is expressed homogeneously in cells of different hemopoietic tissues, we applied FISH to lymph node, peripheral blood and bone marrow samples obtained simultaneously from 23 untreated B-CLL patients. DESIGN AND METHODS: Twenty-three newly diagnosed patients with B-CLL, 15 in stage B and 8 in stage C, were included in the present study. Peripheral blood smears, bone marrow aspirate smears and lymph node touch imprints were collected from each patient at diagnosis. Cytologic preparations were examined by light microscopy in order to assess the lymphocyte morphology. Immunophenotyping was performed by cytofluorimetric analysis of the peripheral blood, bone marrow and lymph node mononuclear cell suspensions. The diagnosis was supported in all cases by histologic findings in bone marrow biopsy and lymph node biopsy specimens. Fluorescence in situ hybridization was performed on smears of blood and aspirated bone-marrow and lymph node touch imprints obtained by fresh tissue apposition. RESULTS: In 6 of the 23 cases (26%) trisomy 12 was clearly present in all tissues examined. A comparative analysis of the three different hemopoietic tissues was performed. A higher percentage of leukemic CD5+CD23+ cells was detected in lymph nodes than in peripheral blood and bone marrow. A significantly higher proportion of trisomic cells was observed in lymph nodes samples than in peripheral blood or bone marrow smears of trisomy 12 positive CLL patients. INTERPRETATION AND CONCLUSIONS: Several previous reports show that only a proportion of malignant B-CLL cells carry trisomy 12 when analyzed by interphase FISH. The higher proportion of +12 cells in lymph nodes than in peripheral blood or bone marrow of CLL patients with trisomy 12 could reflect different cell distributions in different tissues, or lymph node specific tropism, or proliferative advantage in selected tissue. At present, the role of trisomy 12 in the pathogenesis of lymphoproliferative disorders is unclear.

Aged↗
PubMed1999

A novel translocation t(1;7)(p36;q34) in three patients with acute myeloid leukaemia.

Studies of large numbers of patients have enabled the identification of relatively infrequent chromosome changes, such as inv(3)(q21;q26), t(6;9)(p23;q34) and t(8;16)(p11;p11), whose clinico-biological significance is gradually becoming clearer. Translocations involving chromosomes 1 and 7 are relatively rare in myeloid neoplasias, being found in far less than 1% of cases; the rearrangement that occurs most frequently consists of an unbalanced translocation [t(1;7)(p11; p11)], resulting in complete loss of 7q, associated with therapy-related or environmentally-induced high-risk myelodysplasia. We recently observed three cases of acute myeloid leukaemia (AML) with a previously unreported balanced translocation t(1;7) (p36;q34). Case 1 underwent autologous bone marrow transplantation and remains alive in CR; cases 2 and 3 relapsed after 10 and 4 months, respectively. The response to chemotherapy observed in our cases suggests that variable clinical features might be present in the broad cytogenetic category usually referred to as '7q abnormalities' and contributes to an interesting previous observation of prolonged disease-free survival in a subset of AMLs with 7q- as the isolated chromosome change.

Adult↗
PubMed1998

Extramedullary involvement in patients with acute promyelocytic leukemia: a report of seven cases.

BACKGROUND: Extramedullary involvement is only occasionally observed in patients with acute promyelocytic leukemia (APL) but has been said to occur more frequently after treatment with all- trans retinoic acid (ATRA) than after treatment with cytotoxic drugs. In the literature, 37 well-documented cases have been reported. METHODS: The authors report 7 patients with extramedullary APL documented by cytologic, phenotypic, and molecular analyses among 120 adult APL patients referred to two different institutions during a period of 9 years. RESULTS: In this APL series, extramedullary disease (EMD) occurred in 7 of 120 cases (5.8%). The extramedullary sites were the skin in five patients, the central nervous system in one, and the lymph nodes in one. Molecular analysis of the PML/RARalpha rearrangement was performed on four samples of skin and one of CSF; all patients exhibited the same molecular pattern in the bone marrow (BM) and EMD sites. Of 120 patients, 61 were treated with ATRA plus chemotherapy and 59 with chemotherapy alone. Relapses were observed in 38 patients, 6 of whom had EMD; 1 patient had developed EMD at the onset of APL. Of the relapsed EMD cases, 2 of 61 patients had received ATRA plus chemotherapy and 4 of 59 had received chemotherapy alone. CONCLUSIONS: There is some controversy as to whether treatment of APL with ATRA may predispose patients to the development of extramedullary relapse. The data from this study do not contain evidence that EMD may occur more frequently in APL patients treated with ATRA.

Adolescent↗
PubMed1998

The use of ultrasound biomicroscopy in pre-operative evaluation of orbital-blepharal neoformations: report of a case.

In our study we have taken into consideration the use of ultrasound biomicroscopy (UBM) in a case of orbital-blepharal lymphoma. The advantages of this methodology, which is considered a refinement of B scan ultrasonography, compared with other instruments at present available on the market, have been described. We have tried to show how the instrument for biomicroscopic ultrasonography makes it possible to obtain images of the anterior segment of the eye in every detail; it is, therefore, capable of giving us information once only available by means of examining histopathological sections. Apart from the advantages, in this work we have also described the limits of this methodology, which in order to allow an accurate diagnosis must always be accompanied by the traditional ocular echography.

Adult↗
PubMed1998

Biometric pre-operative evaluation of ocular axial length in patients subjected to corneal transplantation.

In cases of keratoconus and consequent penetrating keratoplasty, the refractive requirements of the patient determine the dimensions of the donor button and the receiving wound size. The pre-operative biometric evaluation of the axial parameters may induce the surgeon to choose an oversized button to obtain the right curvature of the cornea and avoid hypermetropia. In this study we present 20 patients transplanted between 1993 and 1995, 13 female, 7 male, aged between 23 and 45 years. These cases demonstrate the utility of this easy and economic technique.

Adult↗
PubMed1998

Echographic follow-up in patients who have undergone sclero-uveotumorectomy.

A-B scan echography provides accurate information on the location, the nature, the extension of a neoplasm and the involvement of neighbouring tissues as well as on the postsurgical evolution. In this study, we intend to give accurate and useful indications to the surgeon concerning conservative surgery and the follow-up after sclero-uveotumorectomy in cases of uveal neoformations. Between January 1988 and June 1996, we examined 46 patients by means of echography before and after sclero-uveotumorectomy.

Decision Making↗
PubMed1998

Evaluation of the echographic contribution to the parasurgical treatment of melanomas of small dimensions.

In this work we underlined the contribution of echography in the parasurgical treatment (photocoagulative) of melanomas of small dimensions. Fourteen patients were examined; some of them were treated with argon laser, others with krypton laser. The echographic examination was performed with the A-B scan technique, naturally accompanied by fluorangiography before and after the operation. An accurate echographic and fluorangiographic follow-up makes it posible to control the evolution of the lesions efficaciously. From this work it is clear how echography gives highly reliable results which allow us, therefore, both to make an adequate therapeutic decision and to evaluate the efficaciousness of the treatment itself.

Adult↗
PubMed1998

Neoplasia-like echographic evidence in retinopathies of several aetiologies: a case report.

In ocular retinal pathology, several aetiological entities showing various clinical and ophthalmoscopic pictures can simulate a tumour. The contribution of echography to the diagnostic research in ophthalmology is really important and the good knowledge of the difficulties and echographic limits is essential. We specifically report a tubercular granuloma clinically and echographically simulating a ciliary-body melanoma.

Ciliary Body↗
PubMed1998

Alterations of the internal reflectivity of extra-ocular muscles associated with several clinical stages of Graves' ophthalmopathy.

In the period between February 1992 and June 1996, the authors performed extra-ocular muscle echobiometry on 163 patients with Graves' disease. The aim of this study is the evaluation of changes occurring in several clinical stages. The authors noted an increase in internal muscular reflectivity in the advanced phases and an irregular structure in the early stages. Controversial results in the literature warrant mastery of the method and further research.

Adult↗