Milk-of-calcium in breast microcysts with adjacent malignancy.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
A Riccardi
Publications and source records attributed to A Riccardi.
Circulating progenitor cell release and functional characterization after topotecan plus G-CSF and erythropoietin in small cell lung cancer patients.
Topotecan is a new antineoplastic agent active in ovarian cancer, with promising activity in small cell lung cancer and predictable toxicity. As a part of our ongoing attempt to optimize the use of disease-specific drugs as circulating progenitor cell (CPC) priming in solid tumors, we have evaluated the effects on CPC release of single-agent Topotecan followed by granulocyte colony-stimulating factor (G-CSF) + human recombinant erythropoietin (rhEPO), together with the cell cycle status of the collected CD34+ cells. Ten pretreated patients with small cell lung cancer received Topotecan (1 mg/m2, i.v. for 5 consecutive days) followed by G-CSF (5 microg/kg/day, s.c.) + rhEPO (10,000 I.U. daily, s.c.), starting 24 h after Topotecan. The combination was well tolerated and no relevant side-effects were recorded. On day +10 (range +9 to +11) after the last dose of Topotecan, the median WBC count and the CD34+ cell peak were 8.2 x 10(3) microl (range 4.9-13.9) and 55 microl (range 28-75), respectively. Using flow cytometry, a detailed cell cycle analysis was performed on these CD34+ cells. The cell cycle distribution was determined by DNA content coupled with bromodeoxyuridine incorporation analysis. Apoptosis was evaluated by quantitating DNA strand breaks. The percentage of CD34+ cells in active S-phase was 10.2+/-5%, while early apoptotic CD34+ cells were detected in a low percentage (5.5+/-3%). Topotecan followed by G-CSF + rhEPO mobilizes CPCs effectively. This sequence exerts a stimulation on CD34+ cell cycle with a protective effect from chemotherapy-induced apoptosis. Taken together, these data could be of value for the incorporation of Topotecan, as well as of the combination of G-CSF and rhEPO, into high-dose chemotherapy programs with CPC support.
Adult↗
Cancer chemotherapy-related thrombotic thrombocytopenic purpura: biological evidence of increased nitric oxide production.
The occurrence of thrombotic thrombocytopenic purpura (TTP) in cancer patients receiving chemotherapy has been well established; although this entity is rare, its clinical importance seems to be growing. We describe 3 cases of TTP developing in cancer patients receiving different chemotherapeutic regimens. Using a sensitive high-performance liquid chromatographic method, we evaluated the stable nitric oxide end products, nitrite and nitrate, in the plasma of these patients. Nitric oxide is one of the key components involved in maintaining the normal nonthrombogenicity of the vascular endothelium. In our 3 patients, we found increased nitrate titers that were substantially higher than those observed in patients with de novo TTP. The observed increased release of nitrate could be interpreted as the consequence of massive disruption of endothelial integrity, with consequent passive nitric oxide release in vivo, or an adaptive mechanism of the endothelium to compensate for diffuse microvascular occlusion. The 2 mechanisms may both be involved, but the normal titers of nitric oxide end products in de novo TTP suggest that the former mechanism is more important, at least in cancer chemotherapy-related TTP.
Antineoplastic Combined Chemotherapy Protocols↗
Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma.
Age could influence the prognosis of multiple myeloma patients treated with conventional chemotherapy. Between January 1987 and March 1990, 341 consecutive previously untreated patients with multiple myeloma received chemotherapy within the prospective, multicentre, randomized Protocol MM87. Survival was evaluated in patients aged > or < or = 66 years (the median age for the whole series) and in a subgroup of patients aged < 55 years. These groups were similar for main clinical characteristics, including results of cytostatic treatment. As of May 1996, 271 (79%) of the 341 patients had died, and median follow-up of the 70 (21%) living patients was 82 months. Overall, younger patients survived longer than older ones. In fact, in patients > and < or = 66 years, median survival was 31 and 44 months (P < 0.00095) and the percentage of patients surviving over 72 months was 17% and 32% (P = 0.0018) respectively; in patients < 55 years, these figures were 57 months and 35% respectively (P = 0.02 and 0.01, with respect to patients aged > 55 years). In all groups, about 50% of the patients surviving over 72 months had stage I disease. For multiple myeloma patients treated with chemotherapy, survival is favourably affected by relatively young age and early stage of disease.
Adult↗
Cranial irradiation and permeability of blood-brain barrier to cytosine arabinoside in children with acute leukemia.
Cranial irradiation (CI) is an effective way to prevent central nervous system (CNS) leukemia in children with acute leukemia (AL). However, it is still unclear whether the antileukemic effect of CI is mediated by alteration of blood-brain barrier (BBB) permeability and consequent increased levels of systemically administered drugs or whether it simply results from a direct cytolytic effect on leukemic cells in the meninges at diagnosis. We evaluated the influence of CI on BBB permeability to 1-beta-D-arabinofuranosylcytosine (ara-C) in 23 children with AL undergoing CI for CNS leukemia prophylaxis. CI was administered at 18 Gy (16 patients) and 24 Gy (7 patients). ara-C levels were measured in cerebrospinal fluid (CSF) and plasma before, during, and after CI. Two doses were evaluated: 75 mg/m2/day (12 patients) and 480 mg/m2/day (11 patients). CSF and plasma ara-C levels were measured when steady state was achieved. CSF:plasma ratios, obtained before, during, and after CI, were compared by an ANOVA model for repeated measures and by Tukey's test. At the 75-mg/m2/day dose, the mean values of ara-C CSF:plasma ratios before, during, and after CI were 0.20, 0.27, and 0.27, respectively. At the 480-mg/m2/day dose, the mean CSF:plasma ratios before, during, and after CI were 0.09, 0.12, and 0.13, respectively. No significant differences were observed when CSF:plasma ratios were compared before and during, during and after, and before and after CI. Our results indicate that CI at the doses used for CNS prophylaxis in AL does not significantly alter the BBB as far as ara-C is concerned.
Adolescent↗
A human neuroblastoma xenograft model for 125-I-metaiodobenzylguanidine biodistribution studies.
We developed an animal model to evaluate the 125-I-metaiodobenzylguanidine (125-I-mIBG) biodistribution in tumor bearing mice. Six weeks old nude-atimic mice were subcutaneously injected with 30 x 10(6) cells of the human neuroblastoma (NB) cell line SH-SY5Y. TE-671, a rhabdomyosarcoma cell line, was used as a control tumor without a specific mIBG uptake mechanism. In order to prevent possible tumor rejection mediated by NK activity the anti asialo GM1 antiserum was administered intraperitoneally once a week for 4 weeks. The maximum anti asialo mediated effect was obtained by administering the first dose the same day as the cell implant. In this group of animals by 9 weeks 98% of mice had a measurable tumor. We have utilized this model to evaluate the biodistribution of 125-I-mIBG given as two different formulations: standard preparation with a specific activity of 84 mCi/mg and the no carrier added (n.c.a) formulation with a specific activity of approximately 8,000 mCi/mg. Our preliminary results indicate that the biodistribution of the two different formulations in the various organs are similar. Therefore it appears that n.c.a. mIBG should not cause an increased toxicity in possible normal target organs such as heart or adrenals. Additional experiments will be performed in this model to ascertain if there is a potential advantage of the clinical use of n.c.a. mIBG over the standard preparation.
3-Iodobenzylguanidine↗
[Long-term follow up of patients surgically treated for pyelo-ureteral disease by the Anderson-Hynes technique].
A series of 48 patients with hydronephrosis (mean age 31 yrs.) underwent on Anderson-Hynes pyeloplasty. Assessment was carried out in 30 pts. after a mean observation time of 90 months, with a minimum 5 years follow-up. Clinical examination, laboratory investigations, renal ultrasonography, urography and renal scan were performed pre-operatively and at follow-up. There was one patient with evidence of stenosis in the ureteropelvic junction; one patient developed urinary leakage post-operatively and required surgical correction. All patients had symptoms pre-operatively and no one had symptoms post-operatively. Four patients had calcolosis associated, postoperatively all pts. were stone free; four years later one patient developed litiasis. We observed that the results of surgical intervention in hydronephrosis are excellent especially in patients aged less than 30 years.
Adolescent↗
Experience with poorly myelosuppressive chemotherapy schedules for advanced myeloma. The Cooperative Group of Study and Treatment of Multiple Myeloma.
In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.
Adult↗
A prognostic index for multiple myeloma.
The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes (with median overall survival of 52, 28 and 13 months respectively) and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient.
Aged↗
Oral idarubicin and prednisone for advanced, previously untreated, multiple myeloma: a pilot study. Cooperative Group of Study and Treatment of Multiple Myeloma.
Explore the source record for details and available documents.
Administration, Oral↗
Cell proliferation and ploidy of human solid tumours: methodological experience with in vivo bromodeoxyuridine and DNA flow cytometry.
A sequential procedure for single and multiparameter flow cytometry (FCM) that allows detailed cell proliferation and DNA ploidy studies of human solid tumours is reported here. This description includes time collection and storage, tissue disaggregation and staining as well as FCM analysis of samples. The overall feasibility, together with some critical aspects of the DNA/bromodeoxyuridine (BrdU) in vivo assay for cell kinetic studies in human solid tumours, are reported, based on our experience in recent years. We found that the BrdU in vivo method, coupled with bivariate FCM for measurements, is a valuable approach for a 'dynamic' assessment of tumour cell proliferation in the clinical setting. Routine measurements can be achieved providing that well standardised tissue disaggregation and immunolabelling procedures are performed. In different solid tumours, cytokinetic results were satisfactory in 85% of cases as far as the BrdU-labelling index is concerned while 70% were acceptable for DNA synthesis time and tumour potential doubling time. Causes of failure are also considered and discussed. In order to guarantee the finest detection of aneuploidy, routine high resolution single-parameter DNA analysis is suggested. Our experience with further improvements in cell kinetic studies based on the possibility of gating the BrdU/DNA analysis for a subpopulation of interest (i.e. cytokeratin-positive cells in epithelial tumours) is also reported.
Bromodeoxyuridine↗
Cell kinetics of CD34-positive hematopoietic cells following chemotherapy plus colony-stimulating factors in advanced breast cancer.
Bone-marrow (BM) hematopoietic precursors are recruited into proliferative activity when colony-stimulating factors (CSF) are sequenced with chemotherapy (CT). Previous studies suggested that further CT can be safely administered only when the increased proliferative activity of these cells has subsided, because most cytostatic drugs selectively damage cycling cells. The safest interval between CSF discontinuation and the start of the next CT course needs to be ascertained in vivo. Thirty patients with advanced breast cancer were treated with an intensified FEC regimen, planned at 21-day intervals, sequenced with granulocyte-macrophage (GM)-CSF (15 patients) or granulocyte (G)-CSF (15 patients). Using flow cytometry (FCM) we evaluated the proliferation kinetics of CD34+ BM hematopoietic progenitors before CT+CSF and at different times after CSF administration was stopped. FEC+GM- and FEC+G-CSF sequences both induced a rapid and sustained increase in the percentage of BM myeloid precursors (BMMP%) and in the cycling status of CD34+BM cells. However, while the BMMP% remained elevated in both cases after CSF were stopped, the enhanced proliferative activity of CD34+ cells decreased more rapidly after GM- than after G-CSF. Using FCM, CD34+ BM-derived hematopoietic presursor cell kinetics is readily evaluated in the clinical setting. The administration of CSF following CT increases both the proliferative activity of CD34+ BM cells and the BMMP%. After CSF were discontinued a kinetic refractoriness of hematopoietic progenitors was more evident after GM-CSF than after G-CSF. These data may be of value in designing clinical trials to avoid cytostatic damage to the BM hematopoietic stem-cell compartment.
Aged↗
Cytotoxicity of paclitaxel and docetaxel in human neuroblastoma cell lines.
Taxanes are an important new class of anticancer agents that inhibit cell division by the unique mechanism of increasing the rate of microtubule assembly and preventing microtubule depolymerisation. Using the colony inhibition assay, we compared the cytotoxicity of paclitaxel and docetaxel in three human neuroblastoma (NB) cell lines, SH-SY5Y, BE(2)M17 and CHP100. Different exposure times (3, 6, 12, 24, 48 and 72 h) and different concentrations ranging from 0.1 nM to 10 microM were tested. Both paclitaxel and docetaxel show antineoplastic activity in human NB cell lines. Taxanes' antitumour activity varied among the different cell lines, CHP100 being the most sensitive and SH-SY5Y the least sensitive. Paclitaxel cytotoxicity appears schedule-dependent, with marked cell kill observed only for exposures of 24 h or longer. Docetaxel cytotoxicity was dependent upon prolonged exposure only in the SH-SY5Y cell line, while an exposure time of 3-6 h resulted in exponential cell kill in the other two cell lines. Docetaxel was more cytotoxic than paclitaxel with a mean ratio of (paclitaxel/docetaxel) IC50 values ranging from 2 to 11. For both taxanes, we observed good correlation between cytotoxic effect and percentage of cells blocked in G2/M phase. A cytotoxic effect occurred at concentrations comparable with those achieved in the plasma of patients treated with these agents in initial clinical trials. The full potential of prolonged infusion or repeated daily administrations of taxanes should be explored in clinical studies, and responses to taxanes in neuroblastoma should be assessed in paediatric phase II studies.
Antineoplastic Agents, Phytogenic↗
Different doses of epirubicin associated with fixed doses of cyclophosphamide and 5-fluorouracil: a randomised study in advanced breast cancer.
Explore the source record for details and available documents.
Aged↗
Pelvic endometriosis: reproductive and menstrual risk factors at different stages in Lombardy, northern Italy.
AIM: To analyse the relationship between reproductive and menstrual factors and different stages of pelvic endometriosis. METHODS: Between 1987 and 1990 a case-control study of risk factors for pelvic endometriosis was conducted. Cases comprised 376 women (median age 32 years) with pelvic endometriosis confirmed by laparoscopy or laparotomy admitted to any one of three clinics in Lombardy, northern Italy. A total of 129 (34.3%) of these women were at stage 1, 76 (20.2%) at stage 2, 96 (25.5%) at stage 3, and 75 (19.9%) at stage 4, according to the American Fertility Society revised classification of endometriosis. Controls comprised 522 women admitted to hospital for acute conditions. RESULTS: The risk of endometriosis decreased with increasing number of births. The estimated odds ratios (OR) were similar in different stages of the disease: for example, compared with nulliparous women, the OR of endometriosis at stage 1 was 0.1 in women who reported two or more births and the corresponding values were respectively 0.1, 0.2, and 0.2 for endometriosis at stages 2, 3, and 4. Cases reported fewer induced abortions than controls: the estimated ORs compared with no induced abortion were 0.4, 0.5, 0.2, and 0.2 in women who reported one or more induced abortions for subsequent stages of endometriosis. Women with irregular menstrual cycles were at less risk of the disease: compared with women who reported lifelong regular cycles the estimated ORs were 0.3, 0.5, 0.5, and 0.3 for disease stages 1-4 respectively. No consistent association emerged between the ages at menarche and at first delivery and the risk of endometriosis. CONCLUSIONS: This analysis provides further evidence that reproductive and menstrual factors are associated with the risk of endometriosis. The observation that early and late stages of the disease share similar epidemiological characteristics suggests an epidemiological (and pathogenetic) continuum between various stages of the disease.
Abortion, Induced↗
[Diagnostic accuracy in transvaginal echography in benign endometrial diseases and its comparison with hysteroscopic biopsy].
Abnormal uterine bleeding is one of the main indications for hysteroscopy in peri-menopausal age. Transvaginal ultrasound allows for an accurate study of the endometrium through the evaluation of thickness, homogeneity. The aim of this retrospective study was the evaluation of transvaginal ultrasound versus hysteroscopy in diagnostic approach to abnormal uterine bleeding in peri- and post-menopause. 130 Women referred to the Department of Obstetrics and Gynecology of the University of Pavia for abnormal uterine bleeding entered the study; all them underwent transvaginal ultrasound and hysteroscopy with directed biopsy, with histological diagnosis of benign endometrial disease. On the basis of endometrial thickness measured at ultrasound, premenopausal patients were divided into two groups, post menopausal patients into three groups, and for each group a comparison between hysteroscopic findings, histological diagnosis and echographic aspect was performed. A 100% correspondence between ultrasound, hysteroscopy and histology was found in the group of subjects with endometrial atrophy, with an endometrial thickness of 2.9 +/- 0.68 at ultrasound; in the remaining groups sensibility and specificity of transvaginal ultrasound seem to be lower. In our experience a cut-off of 4 mm can be established for endometrial thickness measured by transvaginal ultrasound. Values that are below this cut-off point are diagnostic for endometrial atrophy, precluding the need for more invasive examinations: a medical treatment can then be administered. On the contrary, an endometrial thickening of 4 mm or more requires an hysteroscopic examination with directed biopsy and histological diagnosis.
Adult↗
Clinical pharmacokinetics of carboplatin in children.
The present study was undertaken to evaluate in children the plasma pharmacokinetics of free carboplatin given at different doses and schedules and to evaluate the inter- and intrapatient variability and the possible influence of schedule on drug exposure. A total of 35 children (age range, 1-17 years) with malignant tumors were studied. All patients had normal renal function (creatinine clearance corrected for surface body area, above 70 ml min-1 m-2; range, 71-151 ml min-1 m-2) and none had renal involvement by malignancy. Carboplatin was given at the following doses and schedules: 175, 400, 500, and 600 mg/m2 given as as a 1-h infusion; 1,200 mg/m2 divided into equal doses and infused over 1 h on 2 consecutive days; and 875 and 1,200 mg/m2 given as a 5-day continuous infusion. A total of 57 courses were studied. Carboplatin levels in plasma ultrafiltrate (UF) samples were measured both by high-performance liquid chromatography and by atomic absorption spectrophotometry. Following a 1-h infusion, carboplatin free plasma levels decayed biphasically; the disappearance half-lives, total body clearance, and apparent volume of distribution were similar for different doses. In children with normal renal function as defined by creatinemia and blood urea nitrogen (BUN) and creatinine clearance, we found at each dose studied a limited interpatient variability of the peak plasma concentration (Cmax) and the area under the concentration-time curve (AUC) and a linear correlation between the dose and both Cmax (r = 0.95) and AUC (r = 0.97). The mean value +/- SD for the dose-normalized AUC was 13 +/- 2 min m2 l-1 (n = 57).2+ The administration schedule does not seem to influence drug exposure, since prolonged i.v. infusion or bolus administration of 1,200 mg/m2 achieved a similar AUC (13.78 +/- 2.90 and 15.05 +/- 1.44 mg ml-1 min, respectively). In the nine children studied during subsequent courses a limited interpatient variability was observed and no correlation (r = 0.035) was found between AUC and subsequent courses by a multivariate analysis of dose, AUC, and course number. The pharmacokinetic parameters were similar to those previously reported in adults; however, a weak correlation (r = 0.52, P = 0.03) between carboplatin total body clearance and creatinine clearance varying within the normal range was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
A prospective comparison between treatment with phlebotomy alone and with interferon-alpha in patients with polycythemia vera.
Interferon alpha (alpha-IFN) is increasingly used for the treatment of patients affected by polycythemia vera (PV). As prior studies are difficult to interpret in view of the lack of appropriate controls, we undertook a randomized comparison of lymphoblastoid alpha-IFN (alpha n-1 IFN) treatment against venesection treatment alone. In a crossover trial, we treated 22 PV patients alternatively for 5 months each with 3 MU/day sc of alpha n-1 IFN and phlebotomy alone. During IFN treatment, red blood cell count and hematocrit level were well controlled in both trial groups, reducing or eliminating the need for phlebotomy in all patients; furthermore, platelet number and white blood cell count declined during alpha-IFN therapy. In addition, the number of symptomatic patients was greatly reduced, and in six patients a reduction in splenic size was observed. Finally, the only patient with chromosomal abnormalities showed a complete cytogenetic conversion after 5 months of alpha-IFN therapy. Thus, for the first time, our results provide the unequivocal demonstration that alpha-IFN is superior to phlebotomy in controlling the pathologic expansion of erythroid elements and all the clinical aspects of this disease.
Adult↗