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Biomedical subjects

M Forni

Publications and source records attributed to M Forni.

At least 19 recordsLinked to original sources
PubMed2006

Diffuse and focal brain stem tumors in childhood: prognostic factors and surgical outcome. Experience in a single institution.

OBJECTIVE: Brainstem tumors (BSTs) are usually gliomas and are divided into diffuse BSTs (DBSTs) and focal BSTs (FBSTs). The aim of this study is to investigate the different outcomes of these two entities. METHODS: Thirty-one patients with BSTs were admitted to our institution from 1995 to 2003. Patients with DBSTs were treated with locoregional radiotherapy (1.8 Gy/day for 54 Gy) and weekly vincristine for radiosensitization (1.5 mg/sm for six total doses). Patients with FBSTs underwent surgical resection. Chemotherapy and/or radiotherapy were considered in progression. RESULTS AND CONCLUSIONS: Fourteen patients were diagnosed as having DBSTs. The responses to treatment were ten cases of partial response, three of stable disease, and one of progressive disease. General and/or neurological symptoms improved in more than 80% of patients. The median time from diagnosis to progression and to death were, nonetheless, 8 (range of 3-13) and 13 (range of 4-25) months, respectively, with a 2-year overall survival rate of 12.3% [standard error (SE) 11.2]. Seventeen patients were diagnosed as having FBSTs. Gross total removal was achieved in 4/17 cases, subtotal removal in 7/17, and partial removal in 6/17. There was one surgery-related death. Eight out of 17 patients had adjuvant chemo- and/or radiotherapy after progression: 6/8 are without neurological symptoms and 2/8 have died due to tumor progression. The 4-year overall and disease-free survival rates are 87.4 (SE 8.4) and 58.8% (SE 11.9), respectively, the extent of resection being the most important prognostic factor (p=0.012). DBSTs continue to carry a dismal prognosis, thus demanding new treatment modalities; FBSTs can be treated surgically and patients benefit from a better prognosis.

Adolescent↗
PubMed2006

Oral manifestations of langerhans cell histiocytosis in a pediatric population: a clinical and histological study of 8 patients.

Langerhans Cell Histiocytosis is a rare and protean disease of unknown etiology, clinically characterized by single or multiple osteolytic and/or soft tissue lesions. Oral involvement may predate systemic manifestations or mimic infectious/inflammatory disorders. In the present series, oral involvement characterized eight cases of pediatric Langerhans Cell Histiocytosis and oral symptoms represented a very early sign of this disease in four patients. A careful clinical investigation and a proper histologic analysis were required for achieving a definite diagnosis and for confirming clinical suspicion of disease relapse. Immunohistochemistry, that nowadays represents a reliable and accessible ancillary histological technique, allowed the definite diagnosis in all cases of our series.

Child, Preschool↗
PubMed2006

Familial tumoral calcinosis and testicular microlithiasis associated with a new mutation of GALNT3 in a white family.

BACKGROUND: Familial tumoral calcinosis (FTC) is a rare autosomal recessive disease characterised by the development of multiple calcified masses in periarticular soft tissues; GALNT3 gene mutations have recently been described in an African American and in a Druse Arab family with FTC. OBJECTIVE: To report the clinical and histological features caused by a new GALNT3 mutation in a white family. RESULTS: Homozygosity for the nonsense mutation Lys463X was found in both affected siblings, who displayed a classic phenotype, the male also having testicular microlithiasis. He is the first subject described with testicular microlithiasis in FTC. CONCLUSIONS: The high testicular expression of GALNT3 suggests that the gene alteration could act locally by causing deposition of calcium, and the testis may be an underestimated site of calcification in FTC. Autoimmune diseases are present in several members of the family. Although immune disorders have been described in FTC, autoimmunity does not segregate with the GALNT3 mutation in this family.

Autoimmune Diseases↗
PubMed2005

Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs.

Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma.

Animals↗
PubMed2005

Spontaneous blinking behaviour in persistent vegetative and minimally conscious states: relationships with evolution and outcome.

There is evidence that spontaneous blinking correlates with cognitive functions. This arises from the observation that blinking rate (BR) is modulated by arousal levels, basic cognitive processes (e.g., attention, information processing, memory, etc.) and more complex cognitive functions (e.g., reading, speaking, etc.). The aim of this work was to test the role of BR evaluation in the assessment of cognitive network functioning in awake patients with consciousness deficits. Thirteen patients were recruited for the study, and were assessed by the Glasgow coma scale (GCS) and Glasgow outcome scale (GOS) on admittance and discharge, respectively. A level of cognitive functioning scale (LCFS) score was assigned at every change in awareness or at least every 2 weeks. At the same time as the clinical tests, the BR was observed for a 5-min period. Ten healthy subjects, observed throughout three non-consecutive days, formed the control group. The BR underwent a different temporal behaviour in the two diagnostic categories. In the persistent vegetative state (PVS) group it remained stable throughout time and linked with the clinical conditions of the patients; whereas in the non-persistent vegetative state (NPVS) group it decreased over time as the cognitive conditions improved. Moreover, a strong inverse correlation was found between overall BR values and LCFS scores. We have concluded that the blinking behaviour changes manifested in PVS and NPVS patients reflect different evolution phases of a cholinergic-dopaminergic imbalance, and that a reduced BR characterizes the early stages of consciousness recovery.

Adult↗
PubMed2005

Laparoscopic insemination technique with low numbers of spermatozoa in superovulated prepuberal gilts for biotechnological application.

New biotechnologies, such as sperm-mediated gene transfer (SMGT), spermatozoa freezing and spermatozoa sorting have improved the possibilities to produce animals with desirable features. The main problem associated with these technologies is the scarce availability of spermatozoa for insemination. The objective of this study was to develop a laparoscopic insemination (LI) technique in gilt that allows the use of low semen doses resulting in high fertilization rates (FR) and minimal distress to the animal; the efficiency of this technique was compared to conventional artificial insemination (AI). Ten gilts were inseminated 36 h post hCG treatment near both utero-tubal junctions (UTJ) with 1.5 x 10(9)spermatozoa/5 mL per horn and 10 gilts (C) underwent conventional AI. Embryos were collected either at two to four cell stage (LI, n = 5; C, n = 5) for determination of fertilization rate or at day 6 for evaluation of developmental competence (LI, n = 5; C, n = 5). LI gilts showed a slightly higher FR than control animals. In a second trial, 24 gilts underwent LI with varying doses (1.5 x 10(8), 1.5 x 10(7), 1 x 10(7), 5 x 10(6) or 1 x 10(6)) of semen. Two to four stage embryos were collected and FR was evaluated in each tube. FR obtained with the lowest dose was significantly different from that with other dosages (P < 0.05). Embryos were cultured in vitro to blastocyst stages (percentage of blastocysts: 79.2 +/- 3.6%). In a third trial, five gilts were inseminated with semen processed by SMGT technique; both FR (86.1 +/- 9.9%) and transgene protein expression were satisfactory. In conclusion, this study shows that LI can be a useful tool for reducing doses of insemination, without affecting the efficiency of fertilization; this technique could have a wide range of biotechnological applications.

Animals↗
PubMed2005

Exposure to human blood inactivates swine endothelial ecto-5'-nucleotidase.

Ecto-5'-nucleotidase (E5'N) is an extracellular enzyme forming anti-inflammatory and immunosuppressive adenosine. We evaluated whether confrontation of pig heart and endothelial cells with human blood changes the activity of E5'N. Pig hearts were perfused ex vivo with fresh human blood for 4 h. Pig aortic endothelial cells (PAEC) were incubated in vitro with human plasma for 3 h. Ex vivo perfusion of pig heart with fresh human blood resulted in a decrease in E5'N activity to 62% and 61% of initial in wild-type and transgenic pig hearts, respectively. PAEC activity of E5'N decreased to 71% and 50% of initial after 3 h exposure to heat-inactivated and active complement human plasma, respectively, while it remained constant in controls. Pig heart activity of E5'N decreased following exposure to human blood, which may affect adenosine production and exacerbate hyperacute and vascular rejection.

5'-Nucleotidase↗
PubMed2004

Quality specifications for biochemical markers of myocardial injury.

BACKGROUND: The current approach to the diagnosis and monitoring of myocardial damage, recognizes to biochemical markers, and in particular to troponins, a key role being well demonstrated that all elevated values were associated with a worsened prognosis. In 2001, the IFCC Committee on Standardization of Markers of Cardiac Damage published guidelines addressing the quality specifications for troponin assays in order to guarantee an analytical performance satisfying medical requirements and to standardize the quality of commercial methods. We describe how the application of quality specifications may be useful in daily practice, in order to provide advice to clinicians in the investigations of complex clinical cases of patients suffering from myocardial damage. MATERIALS AND METHODS: The samples from three patients (cases 1-3) admitted to the hospital with symptoms suggestive of cardiac disease, showing high troponin I (cTnI) values not correlated with clinical condition, were investigated in order to verify the accuracy of the laboratory data. The standard of quality specifications related to assay specificity, imprecision and interferences were evaluated using different platforms for cTnI assays, carrying out imprecision profile and specific studies on more common interferents in immunoassays. RESULTS: The obtained results allow us to demonstrate two cases of false-positive cTnI values attributable to a macrocomplex between a modified "in vivo" cTnI and immunoglobulin G (case 1) and to a presence of heterophilic antibodies affecting the RxL Dimension procedure (case 3). Instead, the accuracy of data obtained in case 2 was evidenced by the imprecision profile obtained in our laboratory and by the comparison of results between different laboratories using same platform. CONCLUSIONS: The lack of standardization as well as the wide differences in the development of each assay give rise to major concerns regarding cTnI determinations. The laboratory must therefore check the compliance between the analytical characteristics of the method utilised against recommended quality specifications for a reliable understanding of the frequency of false-positive results as well as other serious analytical errors.

Adult↗
PubMed2003

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group.

BACKGROUND: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. PATIENTS AND METHODS: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m(2) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. RESULTS: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). CONCLUSIONS: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance status.

Adenocarcinoma↗
PubMed2002

Role of prolactin, growth hormone and insulin-like growth factor 1 in mammary gland involution in the dairy cow.

Bovine mammary involution, an important process for subsequent lactations, is characterized by loss of epithelial cells by apoptosis, but its hormonal regulation is still not well defined. Prolactin (PRL) and growth hormone (GH) play a specific role on rat mammary gland apoptosis, through insulin-like growth factor 1 (IGF-1) and the IGF binding protein (IGFBP) system. The purpose of our investigation was to determine the possible role of PRL, GH, and IGF-1 on cell survival and on IGFBP-5 expression in the bovine mammary gland. Mammary gland explants were cultured in the presence of cortisol, 17beta-estradiol, progesterone, insulin, PRL, GH, and IGF-1 and with the same treatment but without PRL, GH or IGF-1, respectively. After 24 h of culture, we determined the level of apoptosis through evaluation of DNA laddering in the oligonucleosomal fraction and examined IGFBP-5 messenger RNA (mRNA) expression. The results show a high level of DNA laddering and an increase in IGFBP-5 mRNA content in mammary explants cultured in the absence of PRL, GH, or IGF-I with respect to explants treated with all hormones. Moreover, explants cultured in presence of PRL, GH, or IGF-I show a low level of DNA laddering and IGFBP-5 expression with respect to explants cultured without any hormones. These data demonstrate a relationship between levels of apoptosis and IGFBP-5 mRNA expression in the bovine mammary gland and confirm the involvement of this binding protein programmed cell death and its relationship with the main lactogenic hormones.

Animals↗
PubMed2001

Survival trends of childhood cancer diagnosed during 1970-1994 in Piedmont, Italy: a report from the Childhood Cancer Registry.

BACKGROUND: The Childhood Cancer Registry of Piedmont (CCRP) started its activity in 1967. It is population based and covers the Piedmont Region (population 4,500,000; NW Italy). This article reports on time trends in survival after a childhood cancer diagnosed during 1970-1994. PROCEDURE: During 1970-1994, 2,329 incident cases were registered at CCRP on the basis of histological and/or clinical information, excluding 30 cases reported only by death certificate. Histological or hematological diagnosis was available for 2,067 cases. Vital status was assessed through the offices of the town of residence. At the end of follow-up, 1,202 cases were alive, 1,084 dead and 43 were not traceable. Survival was measured for the major diagnostic groups using both univariate and multivariate statistics. RESULTS: The 5-yr survival rate for acute lymphoblastic leukemia (ALL) improved regularly from 24.7% in 1970-1974 to 81.1% in 1990-1994, for acute nonlymphoblastic leukemia (ANLL) from 0% to 38.1%, for non-Hodgkin lymphoma (NHL) from 25.2% to 67.7%, for tumors of the central nervous system (CNS) (all types) from 33.4% to 75.9% and for Ewing tumor from 0% to 90%. Focusing on survival by period of diagnosis, the highest 5-year survival rate was observed for children diagnosed during 1985-1989 for medulloblastoma, neuroblastoma (NB), retinoblastoma, Wilms tumor, osteosarcoma, and rhabdomyosarcoma and for children diagnosed in 1990-1994 for the remaining sites. The trend over time was statistically significant for ALL, ANLL, NHL, CNS tumors, NB, and osteosarcoma as well as for all malignancies together. CONCLUSIONS: Population-based survival studies are useful complements to clinical studies. Survival results in the present study are similar to those presented for other European countries and the United States. For most types of neoplasm (except CNS) survival probability appears to stabilize 5-10 years after diagnosis.

Adolescent↗
PubMed2001

Prevention of mucositis in bone marrow transplantation: a double blind randomised controlled trial of sucralfate.

Mucositis is still a leading side effect of high dose chemotherapy and irradiation delivered in autologous and allogeneic bone marrow transplantation. In this double blind randomised study, we tested the efficacy of sucralfate for the prevention of mucositis induced by such conditioning treatments. Treatment was started one day before conditioning regimen and patients were prospectively evaluated. The main endpoint was severe mucositis that was more frequent in the placebo group than in the sucralfate group (47% vs. 29%, P = 0.07). This trend was confirmed after adjustment on total body irradiation (TBI) (P = 0.06), the sole stratification parameter. Interestingly, patients receiving sucralfate showed a significant reduction of diarrhoea (25%) vs. 53%, P = 0.005). Overall, the preventive administration of sucralfate appears to be an effective procedure to diminish the occurrence of severe oral and intestinal mucositis in patients treated by high dose chemotherapy alone or combined with TBI before bone marrow transplantation.

Adolescent↗
PubMed2001

Hyperprolactinaemia and prolactin binding in benign intracranial tumours.

BACKGROUND: Meningiomas have been found to have receptors for several hormones, such as oestrogen, progesterone, somatostatin, dopamine and recently also for prolactin. METHODS: To investigate any possible role of prolactin in the growth of those tumours we detected the presence of prolactin-receptors (PRL-R) in 22 meningiomas and we correlated these data with PRL serum levels in patients before surgery. We also studied 13 patients with schwannomas and 7 with other cerebral tumours (4 glioblastomas, 2 ependymomas and 1 astrocytoma). RESULTS: Increased prolactin binding was present in 10 (45.4 percent;) meningiomas, 9 (69.2 percent;) schwannomas and in the patient with astrocytoma. The presence of high PRL levels was present in 6 (27.2 percent;) patients with meningiomas, 8 (61.5 percent;) with schwannomas and in 3 (42.8 percent;) with other tumours. No direct correlation was present between serum PRL levels and PRL binding in all groups. CONCLUSIONS: In conclusion we confirmed the presence of PRL receptors in patients with meningiomas and we have also shown the presence of PRL receptors also in schwannomas. Moreover increased serum PRL were shown in some patients with different tumours of nervous tissue before surgery. Our data could suggest that PRL might have a role in the growth of meningiomas and schwannomas.

Adult↗