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Biomedical subjects

F Bonetti

Publications and source records attributed to F Bonetti.

At least 37 records · Page 2Linked to original sources

Autologous bone marrow transplantation for acute myeloid leukaemia in children using total body irradiation and melphalan as conditioning regimen.

We conducted a phase II study on 19 children with AML in first (10 patients) or second (nine patients) complete remission (CR) treated with ABMT, evaluating the combination of total body irradiation (TBI, 12 Gy in six divided fractions) and high-dose melphalan (140 mg/m2 in single dose) in an attempt to improve antitumour efficacy of conditioning regimen. All patients received cryopreserved and in vitro purged (mafosfamide at a dose of 100 micrograms/ml) bone marrow. The median time from first CR to ABMT was 5 months compared with a median time of 3 months for patients in second remission. One of the 19 patients, transplanted in second CR, died of transplant-related complication 10 days after transplant and another second CR patient relapsed on day +28, before engraftment. Three further patients in second CR relapsed at 6, 6 and 18 months after marrow transplant, respectively, and this determined a relapse rate of 43% in children given ABMT in second CR and 0% for patients transplanted in first remission (P < 0.05). Seventy-two per cent of all patients are projected to be alive and disease-free at 6 years, whereas the event-free survival of patients in first and in second CR is 100 and 44%, respectively (P < 0.05). Although the number of patients does not allow us to draw any firm conclusion, our results are encouraging and suggest that the association of TBI and high-dose melphalan appears to be safe and valuable.

Adolescent

pTNM stage distribution in breast cancer: a population-based survey in northern Italy. Collaborative Group of Pathologists for Cancer Registration in Verona.

AIMS AND BACKGROUND: The role of distribution by stage at diagnosis in breast cancer has been considered in many studies, with particular regard to evaluation of prognosis, impact of screening programs and quality of care. Nevertheless, international comparisons of descriptive data can be hampered by lack of homogeneity in staging methods. The TNM is presently the most common staging system used all over the world, although some criticism have been raised recently against its pragmatic value. The present study reports a population-based survey of pathologic TNM distribution in incident cases of female breast cancer in the Verona province, a geographical area of northern Italy covered by cancer registration. METHODS: All histologically proven incident cases of breast cancer were identified in the study period 1988-1990 and classified as for tumor size and nodal involvement according to the pathological TNM criteria. The type of surgical treatment was also registered for all cases diagnosed in 1990. RESULTS: one thousand two hundreds and fifty-four invasive and in situ breast cancers were observed and pT1 cases accounted for 44.4%. Nodal involvement was present in 41.5% of invasive cancers. A surgical treatment was performed in 1213 patients (96.7%). Axillary dissection was reported in 1080 cases, 820 of them (76.6%) having 10 or more lymph nodes examined. Radical mastectomy accounted for 74% of the 458 breast cancers diagnosed in 1990 and 31.6% of the eligible cases were conservatively treated. CONCLUSIONS: Cancer registries should be encouraged to report data on stage distribution in breast cancer (and in other malignancies). This practice could improve international comparisons and give an essential contribution to studies on survival, screening programs and quality of care.

Adult

Breast solitary schwannoma: fine-needle aspiration biopsy and immunocytochemical analysis.

A case of intramammary solitary schwannoma (SS) (benign neurilemoma) diagnosed by fine-needle aspiration biopsy (FNAB) and supported by immunocytochemical study is reported. The tumor arose in the right breast of an 18-yr-old woman and was clinically and radiologically considered a fibroadenoma. The smears obtained by FNAB of the lump showed clusters of spindle-shaped cells and suggested a benign mesenchymal neoplasm. The presence of some structures reminiscent of Verocay bodies and the immunocytochemical reactivity for S-100 protein antiserum demonstrated the schwannian nature of the tumor and suggested the diagnosis of SS. The final histologic examination confirmed the cytologic diagnosis.

Adolescent

Preoperative diagnostic accuracy of fine-needle aspiration in the management of breast lesions: comparison of specificity and sensitivity with clinical examination, mammography, echography, and thermography in 249 patients.

Two hundred and forty-nine women suffering from breast problems underwent a complete series of tests including clinical examination, mammography, echography, thermography, and fine-needle aspiration (FNA). Ninety-four of these patients were shown to be positive or to have suspected malignancy. Accordingly, they underwent surgical excision followed by histologic examination, while the remaining patients were re-examined after 12 to 18 mo in order to exclude false negatives. The analysis of specificity and sensitivity of every single procedure showed that FNA describes the best degree of sensitivity and specificity but no procedure allows, by itself, the detection of all carcinomas. When considered in combination, clinical examination, mammography, and fine-needle aspiration have a sensitivity of 100% and a specificity of 49%, and are the best diagnostic tests for a correct assessment of mammary lesions. Thermography and echography showed a low degree of sensitivity and should not be included in the routine diagnostic procedure of breast lesions.

Biopsy, Needle

Common acute lymphoblastic leukaemia-lymphoma expressing cytokeratin: a case report.

This report presents a case of common acute lymphoblastic leukaemia-lymphoma expressing low molecular weight cytokeratin but no leukocyte common antigen (CD45) in a 57-year-old man. The unusual morphology and clinical course together with the aberrant immunohistochemical results suggested a diagnosis of undifferentiated carcinoma. A detailed immunohistochemistry study on frozen and paraffin sections and molecular analysis prevented a diagnostic mistake.

Antibodies, Monoclonal

Cathepsin D and E co-expression in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and Langerhans' cell histiocytosis: further evidences of a phenotypic overlap between these histiocytic disorders.

Nosological classification of sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) is difficult, and the normal cellular counterpart of Rosai-Dorfman (RD) cells is uncharacterised. The peculiar S-100+ phenotype of RD cells suggests a relationship with the dendritic cell family. Recent investigations have revealed cathepsin E to be selectively concentrated in antigen-presenting cells, whereas cathepsin D was found to be expressed in cells of macrophage lineage. Cathepsin D and E distribution was investigated by immunohistochemistry in a series of SHML biopsies and in two types of dendritic cell proliferative lesions: dermatopathic lymphadenitis (DL) and Langerhans' cell histiocytosis (LCH). In SHML biopsies, RD cells and monocyte-related elements of the sinuses and pulp coexpressed cathepsin D and E. LCH cells also stained for both these aspartic proteinases. Conversely, in DL cathepsin E and D were localised to separate cells that resembled Langerhans' cells (LC) or macrophages, respectively, in morphology and distribution. Our data outline the peculiar immunophenotype of RD and LCH cells and suggest that caution should be exercised in the identification of their normal cellular counterpart. The common expression of cathepsin D and E and of S-100 protein suggests some phenotypic overlap between SHML and LCH cells, despite their striking morphological divergence.

Cathepsin D

Preoperative diagnosis of renal angiomyolipoma: fine needle aspiration cytology and immunocytochemical characterization.

A preoperative diagnosis of renal angiomyolipoma (AML) is of great importance for a correct management of these patients with this tumor. In fact when the lesion is small and asymptomatic a conservative approach may be considered. We have evaluated the radiographic and fine needle aspiration cytology (FNAB) findings in 8 cases of AML. In 3 cases both radiology and cytology were suggestive of carcinoma and thus the patients underwent surgery. In one case both techniques suggested AML but surgery was performed because the lesion was large and symptomatic. In 4 cases where both radiology and cytology suggested AML no surgery was performed. Follow-up data are consistent with the benign nature of the lesions. The immunocytochemical analysis of the FNAB with a panel of antibodies including keratin, vimentin, actin and HMB-45 was indicative of AML in 7 of 8 cases, including 2 of the 3 cases misdiagnosed as carcinomas. The presence of HMB-45-positive perivascular epithelioid cells in the FNABs was the most significant finding. It is concluded that immunocytochemical analysis of FNAB with this monoclonal antibody panel can increase the accuracy of preoperative diagnosis of AML, and allow consideration of a conservative approach in selected cases.

Actins

Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma--the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC).

We report a comparative study of 3 clear cell tumors of the lung (CCTL) and 3 angiomyolipomas (AML) of the kidney. Morphological analysis shows that the cells of CCTL are identical to the perivascular epithelioid component of AML. Phenotypically they both consistently expressed melanoma-associated antigens recognized by Moabs HMB45 and HMSA-1, while they were negative for HMSA-5. A minority of cells also expressed S-100 protein, vimentin and actin. In addition, one case of CCTL showed mature adipose tissue entrapped in the proliferation, thus suggesting an intermediate form between CCTL and AML. Based on morphological and phenotypical similarities, it is suggested that CCTL and AML belong to the same family of lesions, characterized by the presence of a peculiar muscle cell, expressing different melanoma-associated antigens.

Adult

Expression of p75 chain of IL-2 receptor in the early immunological reconstitution after allogeneic bone marrow transplantation.

Expression of p55 and p75 chains of IL-2 receptor (IL-2R) on the surface of both T and natural killer (NK) circulating lymphocytes was investigated in 14 paediatric patients given allogeneic bone marrow transplantation (BMT) from HLA-identical sibling or partially matched family donors. IL-2-induced proliferative and cytotoxic responses were also studied and all analysis was performed within 45 days from transplant. We found that, early after transplant, the percentage of p55+ and of p75+ peripheral blood lymphocytes (PBL) was not significantly different in patients who had received HLA-identical BMT (p55+ 8.04 +/- 4.87%; p75+ 28.27 +/- 18.85%) compared with healthy controls (p55+ 7.26 +/- 6.17%; p75+ 19.42 +/- 10.49%), while recipients of T cell-depleted marrow included a remarkably high percentage (76-90%) of p75+ PBL, which were mostly CD3- and co-expressed CD56 molecule. Comparable values of p55+ lymphocytes were observed in all patients and controls. However, in contrast to the other two groups, in recipients of T cell-depleted BMT the majority of these cells co-expressed p75 chain and CD56 antigen. IL-2-induced proliferation and lymphokine-activated killer (LAK) activity were detectable in all patients, and their values did not correlate with expression of p55 or p75 chains. Our data suggest that expansion of NK subsets expressing IL-2R chains after T cell-depleted BMT may be related to early reconstitution of natural immunity in the presence of allogeneic stimuli.

Adolescent

Short report: verruga peruana in an Italian traveler from Peru.

We report a case of cutaneous bartonellosis in a 24-year-old Italian woman. Soon after returning from a seven-month stay in a central area of Peru at an altitude of 3,130 meters, she developed high fever, headache, and muscle and joint pain that resolved after antibiotic therapy. Two months later, she presented with disseminated, painless, firm, purple, subcutaneous nodules on the neck, shoulders, legs, left eyelid, and hard palate, some of which developed into vegetating lesions. The diagnosis of bartonellosis was made on the basis of the clinical picture, the patient's medical history, the incubation period, the confirmatory histopathologic findings, and the response to treatment with chloramphenicol (500 mg four times a day for 14 days).

Adult

Pilot trial of combined administration of erythropoietin and granulocyte colony-stimulating factor to children undergoing allogeneic bone marrow transplantation.

We carried out a pilot study to evaluate the combined use of recombinant human erythropoietin (rhEpo) and granulocyte colony-stimulating factor (G-CSF) for accelerating marrow engraftment in children given allogeneic bone marrow transplantation (BMT). Fifteen consecutive children were enrolled in this study; 13 completed it and were evaluable. Using analysis of variance, laboratory and clinical data referring to these children were compared with those of 15 patients previously treated with rhEpo alone and with those of 16 historical controls. Erythroid repopulation, evaluated sequentially through serum transferrin receptor and reticulocyte count, was similarly accelerated in children receiving rhEpo alone and in those receiving combined treatment. These latter, however, showed a further reduction in the total number of red blood cell units required to reach transfusion independence (1.1 +/- 0.7 in the study population vs 2.7 +/- 1.2 in rhEpo group vs 4.2 +/- 2.3 in historical controls; values are mean +/- 1 SD; p < 0.001). Neutrophil engraftment, i.e. time for neutrophils to reach 0.5 x 10(9)/l, was 11 +/- 3 days in children receiving combined treatment, significantly shorter than that of the control groups (16 +/- 3 and 18 +/- 5, respectively; p < 0.001). Acceleration of neutrophil recovery translated into fewer infections: days of fever were significantly reduced in the study population (4 +/- 2 vs 11 +/- 8 vs 15 +/- 6, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes.

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.

Adolescent

Basic fibroblast growth factor in human pheochromocytoma: a biochemical and immunohistochemical study.

Biopsies of human normal adrenal medulla, adrenal pheochromocytoma, and chemodectoma were studied for the presence of basic fibroblast growth factor (bFGF). An immunoreactive M(r) 18,000 bFGF-like molecule was detected both in normal and neoplastic tissues. This molecule was identified as bFGF on the basis of its molecular weight, its affinity for heparin, and its capacity to induce plasminogen activator production in cultured endothelial GM 7373 cells. The levels of immunoreactive and biologically active bFGF appeared to be significantly higher in the extracts of adrenal pheochromocytoma and chemodectoma than in the extracts of normal adrenal medulla. bFGF immunostaining was detectable in the nuclei of chief (Type-I) cells and of endothelial cells both in normal adrenal medulla and in pheochromocytoma. Cytoplasmic bFGF positivity of endothelial cells was also observed in pheochromocytoma but not in normal tissue. The data are in keeping with the hypothesis that bFGF may exert autocrine and paracrine functions in the growth and neovascularization of human pheochromocytoma.

Adrenal Gland Neoplasms

Alcohol drinking among adolescents from town and mountainous areas in north Italy.

Alcohol consumption was investigated among 9th and 13th grade high school students in the town of Brescia (an urban area) and in the Local Health Unit of Breno, a mountainous area in the province of Brescia. A total of 1364 students from Brescia and 1373 from Breno completed an anonymous questionnaire during school time. In both groups alcohol consumption was greater among 13th graders (modal age: 18 years) and males than 9th graders (modal age: 14 years) and females. Beer was the favourite alcoholic beverage, but wine was the most widely consumed daily beverage: among males, about 8% in grade 9 and 15% in grade 13 drank at least one glass of wine every day. The majority of both 9th and 13th graders had more than one type of alcoholic beverage a week, although many females drank beer only. Total alcohol consumption was higher among the mountainous area students than urban students, especially 9th graders, and greater differences were observed in the consumption of beer with respect to wine. The proportion of male students from Brescia and Breno who consumed more than 6 alcohol units a week were, respectively, 17% and 25% in grade 9 and 36% and 42% in grade 13. A higher prevalence of drunkenness was found among the students from the mountainous area with respect to the urban students, especially males. Among 13th grade males, 42% of students from Brescia and 60% from Breno claimed one or more episodes of drunkenness during the year prior to the interview.

Adolescent

Expression of progesterone receptors in solid-cystic tumour of the pancreas: a clinicopathological and immunohistochemical study of ten cases.

A role for sex hormones in the pathogenesis of solid-cystic tumour (SCT) of the pancreas is suggested by its predilection for young fertile women. Controversial data have been provided for the presence of progesterone receptors (PR) and/or oestrogen receptors (ER) in SCT. We report the immunohistochemical detection of PR in ten cases of SCT. Eight were from young women. The remaining two were from a post-menopausal woman and a young boy. All cases showed PR immunoreactivity in the large majority of neoplastic cells, whereas none exhibited ER positivity. In one tumour two types of cell populations were noted, the more anaplastic invasive-type being PR negative, whereas the more typical was PR positive. PR immunoreactivity in the absence of ER may simply reflect a lower sensitivity of ER antibody failing to reveal the biochemically detectable ER, or that the PR in cells of SCT are constitutively synthesized in an oestrogen-independent way, as in T47D breast carcinoma cell line, meningioma cells and some gastric cancer cells. Our findings support the hypothesis of a possible pathogenetic role of progesterone in SCT, independent of the patient's sex and age.

Adolescent

Transdermal nitroglycerin reduces the frequency of anginal attacks but fails to prevent silent ischemia.

OBJECTIVES: The aim of this study was to objectively evaluate the effects of intermittent administration of transdermal nitroglycerin on effort tolerance, frequency of anginal attacks and presence of silent ischemic events that occur during normal daily activities. BACKGROUND: Previous studies have shown that transdermal nitroglycerin patches reduce the incidence of anginal attacks and improve exercise capacity when given intermittently. However, no carefully controlled studies are available on the effects of these preparations (and their dosing schedule) on the occurrence of "silent" ischemic events during unrestricted daily activities. METHODS: Twelve men with chronic stable angina, a positive exercise test result and significant coronary artery disease completed a randomized, double-blind, placebo-controlled trial in which patches were worn either continuously or with overnight (8 h) removal. The effects of treatment were objectively assessed by both treadmill exercise testing and 24-h ambulatory electrocardiographic monitoring. RESULTS: Only the intermittent dosing schedule afforded a small but significant improvement in exercise tolerance and prolonged exercise duration and time to ST segment depression. The frequency of anginal attacks was also reduced by both the continuous and intermittent treatment, but the effects on symptoms were not paralleled by a concomitant reduction in ischemic episodes recorded during ambulatory monitoring. CONCLUSIONS: The results indicate that when used as monotherapy, intermittent transdermal nitroglycerin preparations lessen symptoms but are ineffective for the long-term prophylaxis of silent myocardial ischemia.

Administration, Cutaneous

Disposition of high-dose busulfan in pediatric patients undergoing bone marrow transplantation.

We studied the pharmacokinetics of busulfan (16 mg/kg) in 16 pediatric patients affected by malignant and nonmalignant disorders between 6 months and 19 years of age (mean +/- SD, 5.7 +/- 6.5 years) who were undergoing allogenic (15 patients) and autologous (one patient) bone marrow transplantation. In all children, the conditioning regimen consisted of busulfan given orally at a dose of 1 mg/kg every 6 hours for 16 doses (total dose, 16 mg/kg), associated with other drugs. The pharmacokinetics of busulfan was studied during the 6-hour dosing interval on the third day of therapy by use of a high-performance liquid chromatographic assay. The value for the time to reach maximum concentration, expressed as mean +/- SD, was 1.1 +/- 0.5 hour; maximum concentration was 609.6 +/- 225.3 ng/ml; steady-state concentration was 358.9 +/- 135.5 ng/ml; area under the plasma concentration-time curve was 2153.6 +/- 813.1 ng.hr/ml; oral clearance was 0.535 +/- 0.226 L/hr/kg; and half-life was 2.4 +/- 0.8 hours. Age-related differences in busulfan disposition were observed. The mean busulfan oral clearance in a group of 10 patients with an age range from 6 months to 3 years was 0.619 L/hr/kg, whereas six patients whose ages ranged from 7 to 19 years had a oral clearance of 0.396 L/hr/kg. The half-lives for busulfan during infancy decrease continuously until early childhood but were prolonged in older children. No significant relationship between systemic exposure to busulfan and drug effect was observed.

Administration, Oral