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Biomedical subjects

M Forni

Publications and source records attributed to M Forni.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vitro mucolytic activity of recombinant human deoxyribonuclease on equine tracheobronchial mucus.

The viscosity of the mucus, its DNA concentration and the size range of the DNA were determined on tracheobronchial samples from 11 horses with lower airway diseases before and after incubation with recombinant human deoxyribonuclease (rhDNase). The horses were divided into two groups on the basis of the cytology of the samples: group A (five horses) with more than 60 per cent neutrophils and group B (six horses) with fewer than 50 per cent neutrophils. The mean mucus viscosity and DNA concentration in the preincubation samples were significantly higher in group A than in group B, and there was a correlation between DNA concentration and mucus viscosity in the preincubation samples from group A. Incubation with rhDNase significantly reduced the viscosity of the samples only in group A.

Animals↗
PubMed2000

Searching for rehabilitation articles on MEDLINE and EMBASE. An example with cross-over design.

OBJECTIVE: To analyze the usefulness of MEDLINE and EMBASE biomedical databases in rehabilitation and to identify descriptors and text words necessary to do a comprehensive search. METHODS: We looked for articles published since 1990 relating to neurologic, orthopedic, respiratory, urologic, and rheumatologic rehabilitation. We looked for all descriptors and text words pertinent to rehabilitation and linked them with "cross-over." RESULTS: We found 165 articles in MEDLINE and 159 in EMBASE with an overlap of only 17% of articles. Only 32% of the articles in MEDLINE and 35% in EMBASE were relevant. Of the 214 nonoverlapping articles, 84% were published in journals present in both databases, but were indexed differently. CONCLUSION: At least two databases must be used to ensure a comprehensive literature search. Searching in EMBASE after MEDLINE we gained 25 articles (32%). Bibliographic search in rehabilitation is particularly complex because of the heterogeneity of the subject matter. Cooperation between an information professional and a clinician is essential to ensure a comprehensive search.

Cross-Over Studies↗
PubMed2000

Vascular endothelial growth factor production in growing pig antral follicles.

Angiogenesis is the process that drives blood vessel development in growing tissues in response to the local production of angiogenic factors. With the present research the authors have studied vascular endothelial growth factor (VEGF) production in ovarian follicles as a potential mechanism of ovarian activity regulation. Prepubertal gilts were treated with 1250 IU equine chorionic gonadotropin (eCG) followed 60 h later by 750 IU of human chorionic gonadotropin (hCG) in order to induce follicle growth and ovulation. Ovaries were collected at different times of the treatment and single follicles were isolated and classified according to their diameter as small (<4 mm), medium (4-5 mm), or large (>5 mm). VEGF levels were measured in follicular fluid by enzyme immunoassay, and VEGF mRNA content was evaluated in isolated theca and granulosa compartments. Equine chorionic gonadotropin stimulated a prompt follicular growth and induced a parallel evident rise in VEGF levels in follicular fluid of medium and large follicles. Analysis of VEGF mRNA levels confirmed the stimulatory effect of eCG, showing that it is confined to granulosa cells, whereas theca cells maintained their VEGF steady state mRNA. Administration of hCG 60 h after eCG caused a dramatic drop in follicular fluid VEGF that reached undetectable levels in 36 h. A parallel reduction in VEGF mRNA expression was recorded in granulosa cells. The stimulating effect of eCG was also confirmed by in vitro experiments, provided that follicles in toto were used, whereas isolated follicle cells did not respond to this hormonal stimulation. Consistent with the observation in vivo, granulosa cells in culture reacted to hCG with a clear block of VEGF production. These results demonstrate that while follicles of untreated animals produce stable and low levels of the angiogenic factor, VEGF markedly rose in medium and large follicles after eCG administration. The increasing levels, essentially attributable to granulosa cells, are likely to be involved in blood vessel development in the wall of growing follicles, and may play a local key role in gonadotropin-induced follicle development. When ovulation approaches, under the effect of hCG, the production of VEGF is switched off, probably creating the safest conditions for the rupture of the follicle wall while theca cells maintained unaltered angiogenic activity, which is probably required for corpus luteum development.

Animals↗
PubMed1999

Phase I study of high-dose epirubicin in platinum-pretreated patients with ovarian carcinoma.

BACKGROUND: In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines. However, this dose-response question for doxorubicin was never carefully addressed in OC patients. These data and the more favorable toxicity profile of the anthracycline analogue epirubicin prompted us to study high-dose epirubicin (HDE) in relapsed OC patients. PATIENTS AND METHODS: This phase I study included 19 OC patients with measurable or evaluable disease and no more than one prior (cisplatin-containing) chemotherapy regimen. Dose escalation was not allowed in individual patients. Epirubicin was administered by rapid intravenous infusion (<5 min) once every 3 weeks and studied at the following dose levels: 120, 135, 150, 180 and 200 mg/m2 (at least 3 patients per dose level). None of the patients received hematopoietic growth factors. We defined the maximum tolerated dose (MTD) as the dose at which we observed WHO grade 4 hematologic toxicity in >/=50% and/or WHO grade 3 nonhematologic toxicity in >/=30% of the patients. RESULTS: The MTD was 200 mg/m2, with DLT being both hematologic (leukopenia and/or thrombocytopenia) and nonhematologic (mucositis). Objective responses were observed in 6 patients (response rate 32%), 3 of them occurring in 10 patients with primary platinum resistance. CONCLUSIONS: HDE is tolerable and has activity in second-line after cisplatin-based chemotherapy in OC patients. The recommended dose for phase II trials in such patients is 150 mg/m2, with escalation to 180 mg/m2 if toxicity permits.

Adult↗
PubMed1997

Prolactin receptors in human meningiomas: characterization and biological role.

Sixty cerebral meningioma specimens obtained at surgery from 34 female and 26 male patients were examined for the presence of prolactin (PRL) receptors. These were compared with normal arachnoid tissue from which these tumours arise. PRL receptors were detected in 61.7% of meningiomas whereas no PRL binding was found in samples of normal arachnoid tissue. No relationship was found when sex or histological findings were compared with the presence of PRL receptors. Receptor-positive tumours had saturable and high-affinity (Kd, 4.8 +/- 0.5 ng/ml) receptors with hormonal specificity for human PRL (hPRL) resembling that of other target tissues of PRL in man. The biological role of these receptors was investigated in primary cell cultures derived from meningioma tissue characterized for PRL receptor. When human PRL was added to the culture medium, in doses ranging from 1 to 200 ng/ml, a dose-dependent stimulation of 3H-thymidine incorporation was observed only in PRL-receptor positive tumours. The PRL concentrations required to produce a half-maximal effect ranged from 11 to 20 ng/ml and were quite close to the dissociation constant (Kd) of binding of PRL to its receptors. PRL also caused an increase of cell number compared with control with a significant effect after 3 and 4 days of culture. In conclusion, these findings indicate that a large number of human meningiomas express specific and functional receptors for PRL which are involved in mediating its proliferative effects.

Adult↗
PubMed1997

Family treatment of symptomatic children with Helicobacter pylori infection.

BACKGROUND: Familial clustering of Helicobacter pylori infection has been reported. We tested the hypothesis that simultaneously treating all Helicobacter pylori positive family contacts of infected symptomatic children results in lower treatment failure. METHODS: Relatives of 47 children (index) with Helicobacter pylori gastritis had endoscopy to assess prevalence of infection in first degree cohabiting relatives. Controls included 60 children with dyspepsia and Helicobacter pylori gastritis whose infected family contacts were not treated. Index children, siblings younger than 18 years of age and control children received a 2-week course of amoxicillin and tinidazole. Parents of index children and their siblings over 18 years of age received a 2-week course of Colloidal Bismuth Subcytrate and tinidazole. The eradication rate in index children and their relatives was compared to controls whose infected family contacts were not treated. RESULTS: Helicobacter pylori was found in 67% of 31 siblings younger than 18, in 82% of 22 siblings older than 18 years, and in 87% of 92 parents. Endoscopy, repeated four to six weeks after the end of treatment, showed Helicobacter pylori eradication in 94% of children and siblings younger than 18, and in 70% of parents and siblings over 18 years in the family treatment group, compared with 75% of control children (p < .01). CONCLUSIONS: The high prevalence of the infection in family members suggests that person-to-person spread of Helicobacter pylori takes place. Furthermore our results show that if (or when) required, simultaneous treatment given to the whole family results in lower treatment failure, since it may promote compliance to treatment.

Adolescent↗
PubMed1996

In situ detection of apoptosis in regressing corpus luteum of pregnant sow: evidence of an early presence of DNA fragmentation.

Luteolysis has been shown to be correlated with apoptosis in rats, sheep, and cows. In pigs, apoptosis has already been demonstrated as regards atretic follicles. The present study has been conducted to evaluate whether apoptosis occurs during corpora lutea regression in the pregnant pig and to investigate the temporal relationship between apoptosis and functional luteolysis. The apoptotic process has been studied through the research of oligonucleosome fragmentation by means of classical electrophoresis methods and by in situ detection on histological luteal sections. The latter method allows the identification of apoptosis and the localization of apoptotic cells. Pregnant sows were cloprostenol (PGF2 alpha analog) treated and ovariectomized 0, 6, 12, 24, 48, and 72 hr after treatment. Corpora lutea were utilized for progesterone and DNA extraction and in situ evaluation of apoptosis. Clear evidence of apoptosis was seen earlier with the in situ technique (6 hr for stromal tissue, 12 hr for luteal cells) than with the classical method (24 hr). Apoptosis was, however, apparent after plasma and tissue progesterone had reached basal levels. In conclusion, these results are consistent with the hypothesis that apoptosis occurs during luteolysis in pigs. Moreover, the data obtained with the in situ technique made it possible to identify signs of structural regression in stromal tissue first than in parenchymal cells. A two-stage activation of apoptosis has been discussed to explain structural changes that occur during luteolysis after cloprostenol treatment in swine corpora lutea.

Animals↗
PubMed1996

Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer.

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.

Administration, Oral↗
PubMed1996

Immunohistochemical analysis of c-Fos and c-Jun in retinoblastoma.

The c-fos promoter is negatively regulated by the retinoblastoma (Rb)-susceptibility-gene-encoded protein as well as by other genes involved in the control of transcription, cell cycle regulation and neoplastic transformation. We have examined by immunohistochemistry the c-Fos and c-Jun proteins in five cases of retinoblastoma in order to evaluate eventual alterations in their expression in vivo, possibly related to a gene mutation or to loss of Rb negative control.

Animals↗
PubMed1996

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation.

BACKGROUND: The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. PATIENTS AND METHODS: 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm i.v. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accelerator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. RESULTS: 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TTF) and survival. Only 51/118 (43%) patients in remission received WAR. Early-stage patients <= 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. CONCLUSIONS: PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.

Adult↗
PubMed1995

High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience.

BACKGROUND: A dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines has been demonstrated in vitro. However, this has never been carefully addressed in the clinic. These data and the more favourable toxicity profile of the anthracycline analogue epirubicin were reasons to study high-dose epirubicin (HDE) in OC patients who relapsed on/after platinum-based chemotherapy. This was done both in a phase I/II feasibility study (n = 27; HDE dose 120-200 mg/m2 q3 weeks) and a still ongoing straightforward phase II study (n = 91; HDE dose 150-180 mg/m2 q 3 weeks). RESULTS: Responses were observed at all dose levels. Overall 24 of the 118 patients responded (20%), which is much higher than reported with lower doses (7% with doses of 60-110 mg/m2). The most important side effects were myelosuppression, alopecia, nausea and vomiting and mucositis. CONCLUSION: HDE is tolerable and has activity in second-line after platinum-based chemotherapy in OC patients.

Adult↗
PubMed1994

Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants.

To evaluate the efficacy of vaccinations with cytokine-gene-transduced tumor cells, BALB/c mice were challenged with 1 x 10(5) parental cells of a syngeneic adenocarcinoma cell line (TSA-pc). No protection was observed in mice immunized 30 days earlier with 1 x 10(5) nonreplicating mitomycin-C-treated TSA-pc alone, or with Corynebacterium parvum or Complete Freund Adjuvant (CFA). Ten to 30% of mice immunized with nonreplicating cells engineered to produce interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene were protected. Fifty % of mice immunized with replicating TSA-pc admixed with C. parvum and 80-100% of mice immunized with replicating tumor cells transduced with IL-2, IL-4, IL-7, IL-10, or gamma-interferon gene were protected. No cure was afforded by TSA cells admixed with C. parvum or CFA, nor by TSA cells engineered with IL-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha gene injected starting 1 day after TSA-pc challenge. Complete tumor regression, however, was obtained in 10-20% of mice treated with TSA cells transduced with IL-2, IL-4, IL-7, or IL-10 and in 30% of those treated with TSA cells transduced with gamma-interferon gene.

Adenocarcinoma↗
PubMed1994

Transduction of the IL2 gene into human acute leukemia cells: induction of tumor rejection without modifying cell proliferation and IL2 receptor expression.

BACKGROUND: Previous studies have suggested that some of the limitations associated with the administration of high-dose exogenous interleukin 2 (IL2) may be overcome, at least partly, by cytokine gene transfer modalities. These findings have prompted investigations into whether human tumor cells may be transduced with the IL2 gene and whether tumor cell lines could be engineered to release IL2. PURPOSE: The purpose of this study was to evaluate the possibility of inducing a productive transfer of the IL2 gene into human acute leukemia cells and to assess the phenotypic and proliferative changes generated in the engineered cells, as well as their tumorigenic potential in nude mice. METHODS: Three retroviral vectors (DC/TK/IL2, DC/AD/R/IL2, and N2/CMV/IL2) carrying the IL2 gene were used to transduce three human leukemic cell lines: K562 and U937 (myeloid) and ST4 (lymphoid). Messenger RNA expression of the IL2 gene was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and productive IL2 release using a human IL2 assay and an enzyme-linked immunosorbent assay kit. The expression of the p55 (alpha) and p75 (beta) chains of the IL2 receptor were determined by RT-PCR and indirect immunofluorescence. The kinetics of in vitro growth and proliferation of parental and engineered cells were also measured. Parental and IL2 gene-transduced ST4 lymphoblasts were injected into immunosuppressed nude mice that had their tumors measured twice weekly. RESULTS: The productive insertion of the IL2 gene was achieved in all three cell lines studied. The amounts of IL2 constitutively released by the engineered neoplastic cells ranged between 1 and 11 U/mL of IL2 produced from 10(6) cells in 72 hours. A fivefold increase in IL2 production was obtained in ST4 cells by further limiting dilution cloning of the bulk-infected cells. The stable integration of the IL2 gene did not modify the phenotype of the leukemic cells, the expression of the IL2 receptor alpha and beta chains and of several cytokine genes, or the kinetics of in vitro growth and proliferation. In nude mice injected with various IL2-producing ST4 clones, tumor growth associated inversely with the amounts of IL2 secreted by the leukemic cells. CONCLUSIONS: The results of this study demonstrate that the IL2 gene can be productively transduced into human myeloid and lymphoid leukemic cells without modifying their phenotypic and proliferative properties and that this transduction leads to a reduced or abrogated in vivo tumorigenic potential.

Acute Disease↗