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Biomedical subjects

M Giovannini

Publications and source records attributed to M Giovannini.

At least 19 recordsLinked to original sources

Phase II study of the efficacy and safety of cisplatin-epinephrine injectable gel administered to patients with unresectable hepatocellular carcinoma.

PURPOSE: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured < or = 7 cm, total tumor volume < or = 200 cm(3)). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. RESULTS: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. CONCLUSION: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.

Adult↗

Phase analysis of superconducting polycrystalline MgB(2).

Superconducting MgB(2) ceramics were prepared and yield superconducting transition temperatures of about 39 K. For covering the various length scales on which inhomogeneities appear in MgB(2), electron-probe micro-analysis (EPMA) and analytical transmission electron microscopy (TEM) were applied for a phase analysis. Particularly useful were the preliminary electron spectroscopic imaging (ESI) results in the TEM. It could be shown by EPMA that the microstructure consists of a Mg-B-O matrix and boron-rich secondary phases of composition close to MgB(12). It was unclear in which form oxygen was present in the superconducting matrix. By combining the acquisition of B-K and O-K edge jump ratio images and energy-dispersive X-ray spectroscopy in the TEM, we could prove that the matrix consists of superconducting MgB(2) and MgO. Most of the MgO precipitates and grains appear with diameters between 20 and 300 nm. The size distribution of MgO was inhomogeneous and oxygen-rich areas of dimensions >1 microm were also observed. Edge jump ratio images obtained by ESI were analysed for determining the signal values and effects of multiple inelastic scattering.

Boron Compounds↗

Drainage of deep pelvic abscesses using therapeutic echo endoscopy.

BACKGROUND AND STUDY AIMS: The purpose of this study was to evaluate the clinical efficacy of endosonographically guided transrectal aspiration and drainage by plastic stent of deep pelvic abscesses, using a therapeutic echo endoscope device. PATIENTS AND METHODS: Between September 2000 and June 2001, 12 patients (nine men, three women, mean age 67 years) were treated for a perirectal or a pelvic abscess using an endoscopic ultrasound (EUS) technique. The drainage of these fluid collections was performed under EUS guidance, using therapeutic EUS scopes with a large working channel. RESULTS: No major complication occurred during this study. Transrectal stent insertion succeeded in nine patients. In three patients, only aspiration was possible. Among the nine patients in whom a stent was successfully introduced into the fluid collection, complete drainage without relapse was achieved in eight patients (mean follow-up 10.6 months, range 6-14 months). The stent was removed endoscopically after 3 to 6 months. Drainage was incomplete in one patient (with a large abscess, diameter > 8 cm), who subsequently underwent surgical drainage. However, two out of the three patients in whom aspiration alone was performed developed a recurrence of the abscess and required surgical treatment. CONCLUSION: EUS-guided drainage of deep pelvic abscesses could offer an alternative treatment to surgery in the management of these postoperative complications.

Abscess↗

Monitoring breastfeeding rates in Italy: national surveys 1995 and 1999.

AIM: To assess and compare the rates of initiation and duration of breastfeeding in Italy in 1995 and 1999, and to examine the adherence to the ten steps to successful breastfeeding recommended by WHO. METHODS: Two cohorts of mothers who delivered healthy infants in November 1995 (n = 1601) or November 1999 (n = 2450) were interviewed by telephone within 4 wk of delivery and when their infant were 3, 6, 9 and 12 mo of age. Type of breastfeeding was classified according to the WHO definitions. Adherence to the WHO ten steps was evaluated as experienced by the mothers. RESULTS: Initiation and duration of breastfeeding increased during the 1995-1999 period (p < 0.0001). The rate of breastfeeding at birth, at discharge and when the infants were 3, 6, 9 and 12 mo of age was 85%, 83%, 42%, 19%, 10% and 4%, in 1995 and 91%, 89%, 66%, 47%, 25% and 12% in 1999. The rate of exclusive breastfeeding was higher in 1999 than 1995 at birth (39% vs 30%, p < 0.0001) and at discharge (77% vs 70%, p < 0.0001), but overall no longer duration was observed in 1999. At 4 and 6 mo of age the rate of exclusive breastfeeding was 25% and 8% in 1995 and 31% and 5% in 1999. The adherence to each WHO step was higher in 1999 than in 1995 (p < 0.05) but concomitant adherence was low (<3%). CONCLUSION: Although an increase in initiation and duration of breastfeeding occurred in Italy during the 1995-1999 period, the duration of breastfeeding and exclusive breastfeeding is currently unsatisfactory, as is adherence to the ten steps specified by WHO. Promotion of breastfeeding and education and improvement in adherence to the WHO recommendations are still needed in Italy.

Age Factors↗

Concentrations of dioxins and other organochlorines (PCBs, DDTs, HCHs) in human milk from Seveso, Milan and a Lombardian rural area in Italy: a study performed 25 years after the heavy dioxin exposure in Seveso.

AIM: To investigate whether those who were exposed to high levels of the dioxin TCDD 25 years ago in Seveso, northern Italy still have higher than the expected levels of dioxins in their fat stores, and to investigate the concentrations of dioxins in the breast milk of mothers in Seveso and in two other regions in Italy. The load of vertically transmitted dioxins to the next generation, if being breastfed, was also investigated. METHODS: As there may be a synergistic effect of mixtures of organic chlorines, the concentrations of pesticides such as DDTs and PCBs have also been studied in the same human milk samples. Breast milk from 12 mothers from Seveso, Central Milan and a Lombardian village was collected for analysis during the first week and 1 and 3 mo after delivery. Individual samples were used for the analysis of pesticides and PCBs, whereas dioxins were analysed in pooled samples from all 12 mothers on each occasion. RESULTS: In human milk from Seveso, the TCDD concentration in fat calculated on a fresh weight basis was more than twice as high as the level in the other two regions, whereas the concentrations of investigated other toxins were lower in Seveso possible due to induction of the enzyme cytochrome P4501A, which means that the total level of dioxins was the same in all three locations. The congener profile, measured as mean toxic equivalency (TEQ) values, was the same in the Italian samples as previously reported from Stockholm. The calculations are based on the most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher in the samples from Milan than in the samples from the other two Italian regions, which may be due to the fact that, to a greater extent than in the other regions, Milanese food is imported from countries where DDT is still used as a pesticide. CONCLUSION: Twenty-five years after the dioxin catastrophe, human milk from mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD that are more than twice as high as those in central Milan and a Lombardian village. This means that breastfed infants in Seveso still store an appreciable amount of TCDD in their body fat. The health consequences of this fact remain to be elucidated. The effect of the high load of DDTs in central Milan also has to be considered

Adult↗

Long term effects of long chain polyunsaturated fats in hyperphenylalaninemic children.

Blood fatty acid status and visual function of 20 treated hyperphenylalaninemic (HPA) children, randomly allocated into two groups to receive supplementation of either long chain polyunsaturated fatty acids (LCPUFA), including docosahexaenoic acid (DHA), or placebo for 12 months, have been investigated three years after the end of the treatment. Although in the LCPUFA group blood DHA levels and P100 wave latency improved at the end of supplementation, they had returned to baseline after three years.

Adolescent↗

Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon.

BACKGROUND: Crohn's disease is one of the principal human chronic inflammatory bowel diseases. Although its aetiology is still unknown, its complex pathogenesis has environmental, immunological, and genetic determinants. CARD15 is the first susceptibility gene implicated in the predisposition to Crohn's disease and is known to be expressed only in monocytes. However, its expression in situ has not yet been studied. AIMS: To analyse the tissue distribution of CARD15 and identify cells producing CARD15 in samples of colon from patients with Crohn's disease and control subjects. PATIENTS AND METHODS: We analysed CARD15 gene expression in surgical specimens of colon from eight children with Crohn's disease and nine controls by immunohistochemistry, in situ hybridisation, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We showed that CARD15 was present only in the cytoplasm of macrophages in the normal colon. Increased CARD15 expression was detected in Crohn's disease lesions. There were more CARD15 positive cells in Crohn's disease lesions than in uninvolved areas. Both intestinal epithelial cells, macrophages, and their derivatives overproduced CARD15 in Crohn's disease. To further assess CARD15 expression by intestinal epithelial cells, we performed RT-PCR on freshly isolated intestinal epithelial cells, and showed that these cells isolated from Crohn's disease samples contained more CARD15 mRNA than intestinal epithelial cells from controls. CONCLUSIONS: We have demonstrated that colonic involvement in active Crohn's disease is associated with increased CARD15 gene expression in both macrophages and intestinal epithelial cells. Therefore, this deregulation can affect the host-environment interaction and thus contribute to the pathogenesis of this disease.

Acute Disease↗

[Respiratory diseases in infants hospitalized during the 1st 2 years of life for viral lower respiratory tract infections: a one-year follow-up].

BACKGROUND: Epidemiologic data suggest strong links between hospitalisation with bronchiolitis in infancy and subsequent higher risk of developing lower respiratory tract infections (LRTI) and/or hyperreactive airway diseases. The aim of this study was to evaluate in an Italian population the natural history of respiratory diseases in children hospitalised for LRTI when they were <2 years. METHODS: An observational, perspective, longitudinal study was performed through telephone interviews. Nine pediatric tertiary care centres participated to the study evaluating a population of 187 children, hospitalised in the previous year (November 1999-April 2000) for bronchiolitis or pneumonia when they were <2 years of age and participated to a previous study on the prevalence of infant LRTI in Italy (RADAR). RESULTS: Twenty-three (12.3%) children had a gestational age <36 weeks. In the 12 months following the first hospitalisation, an elevated frequency of respiratory symptoms was found. Indeed, 152 (81.3%) children suffered from not-requiring-hospital-admission respiratory infections and 21 (11.2%) were hospitalized again for LRTI: 11.6% had bronchiolitis, 23.5% bronchitis and 35.2% pneumonia. In addition, 1.2% had gs;3 infectious episodes and 21.4% gs;6: 68 (36.4%) showed wheezy bronchitis and 17 (9.1%) were reported to have asthma; 132 children (71%) took antibiotics during the last year, 19.4% >3 times; 111 (59.4%) bronchodilators and 49 (26.2%) oral corticosteroids. One year after the first hospitalisation, 19 subjects (10.2%) were found to be positive to at least one class of allergens by prick test or RAST. CONCLUSIONS: Thus, the demonstration of a high morbidity rate for LRTI, wheezing and asthma in this study group during the first year follow-up after hospital admission further support the need for prophylactic interventions to reduce the morbidity and severity of sequelae of LRTI, in particularly in premature children and/or with additional risk factors.

Anti-Bacterial Agents↗

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Acute Disease↗

Effect of Sildenafil on hypertensive lower oesophageal sphincter.

BACKGROUND: Sildenafil relaxes the muscle cells of the penis arterioles by inhibiting phosphodiesterase-type 5 (PD-5), inactivating the nitric oxide-stimulated cyclic guanosine monophosphate. We investigated whether this effect of Sildenafil is also displayed on the muscles of the hypertensive lower oesophageal sphincter (LES). METHODS: In 14 patients with symptomatic hypertensive LES, oesophageal motility was recorded by means of a low-compliance manometric system with five manometric ports for the oesophageal body and a sleeve for the sphincter. After a basal period of 60 min a tablet of Sildenafil 50 mg (group A; seven patients) or one of placebo (group B; seven patients) ground and dissolved in 20 cc of water was infused in the stomach, randomly and in double-blind manner. Recording continued for a further 60 min. Sphincter tone and pressure wave amplitude were measured each minute and the values averaged for each 5-min period for the post-infusion period of 60 min. The values of the whole post infusion period, the lowest values among the 5-min periods (nadir values) and the values of the last 5-min periods were compared with the basal values in each group, and those of group A were compared with the corresponding values of group B. RESULTS: Sphincter tone and wave amplitude showed after Sildenafil a significant decrease comparable that of the basal period and the placebo. The inhibitory effect reached its maximum 10 min after the infusion and lasted approximately 1 h. CONCLUSIONS: Sildenafil inhibits the lower oesophageal sphincter tone and pressure wave amplitude of patients with symptomatic hypertensive LES. These findings suggest a clinical application of PD-5 inhibitors in the treatment of spastic oesophageal motor disorders.

Adult↗

A phase II single institutional experience with preoperative radiochemotherapy in pancreatic adenocarcinoma.

BACKGROUND: Resection of pancreatic adenocarcinoma has a limited impact on survival. We hypothesized that delivering preoperative radiochemotherapy (RTCT) might enhance local control of the cancer and improve survival. METHODS: Nineteen patients with localized pancreatic cancer (14 head and 5 body) were treated during the past 4 years with an intramural protocol consisting of continuous infusion of fluorouracile (5-FU: 650 mg/m(2)/D1-D5 and D21-D25 and Cisplatin 80 mg/m(2)/bolus D2 and D22 with preoperative external beam radiotherapy (RT) (30Gy split course RT or 45 Gy standard fractionation RT). RESULTS: Four patients did not have surgical resection: Three patients were noted to have liver metastases and 1 patient developed peritoneal carcinomatosis. The remaining 15 patients had potentially curative resection (12 Whipple procedure and 3 distal subtotal pancreatectomy). There was no postoperative death. Pathologic findings showed five major responses including 2 patients with complete pathologic response. The overall median survival for the 19 study patients was 20 months. The median disease free and 2-year overall survival for the group with resection were 30 months and 52.3%. CONCLUSIONS: Preoperative RTCT followed by resection is well-tolerated and safe for patients with localized pancreatic cancer. Major histological response occurred for 25% of patients. This approach could offer improvement in patient survival.

Adenocarcinoma↗

Phenylalanine hydroxylase mutations and phenylalanine-tyrosine metabolism in heterozygotes for phenylalanine hydroxylase deficiency.

UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Parents of patients affected by PAH deficiency (n = 25) detected through the Italian Neonatal Screening Program and referred from January 1994 to June 2000, and parents of healthy children were investigated. In total, 68 subjects without any disease, 34 hyperphenylalaninaemia (HPA) heterozygous parents and 34 age- and gender-matched controls, were recruited. Plasma concentrations of Phe and Tyr in fasting and semifasting (1600 mg Phe oral load) conditions were the main outcome measures. DNA analysis for PAH mutations was performed in all 68 subjects. Compared with controls, heterozygotes showed higher fasting and semifasting Phe concentrations (p < 0.0001), lower semifasting Tyr concentrations (p = 0.015), lower Tyr variations (p = 0.003) and a higher Phe/Tyr ratio (p < 0.0001) in switching from fasting to semifasting conditions. Heterozygotes carrying a severe mutation showed semifasting plasma Tyr concentrations lower than controls (p = 0.019) but not significantly different from Tyr levels found in non-severe carriers (p = 0.197). The Tyr variations were minor in severe carriers than controls (p < 0.001) and non-severe carriers too, although with lower significance (p = 0.089). In six carriers of A403V mutation, parents of mild hyperphenylalaninaemics on an unrestricted diet, significant differences in variations from fasting to semifasting conditions were found compared with parents of patients on a diet. CONCLUSION: Although the great heterogeneity of PAH mutations limits any general conclusion, the results suggest that monitoring plasma Tyr variations may be more sensitive than plasma Phe in assessing the severity of PAH mutations in HPA heterozygotes.

Adult↗

Prolonged breast-feeding (six months or more) and milk fat content at six months are associated with higher developmental scores at one year of age within a breast-fed population.

Since dietary fats may affect brain composition and function in early life, we evaluated developmental indices at 1 year of age in relation to the duration of breast-feeding and the milk fat composition in a breast-fed population. A blinded monitor administered the Bayley test (2nd edition) to 1-year-old subjects born at term and exclusively breast-fed for at least 3 months. Weaning foods were introduced from the 5th month onward. Mothers' milk lipid composition (fat [wt/dL], fatty acid [wt/dL], FA% [% of total fatty acids]) was determined at 0, 1, 3, 6, 9, and 12 months. Statistics used were Student's t-test, Pearson's r, and multiple regression. Forty-four infants out of 95 recruited at birth met inclusion criteria. There was a progressive reduction of the number of breast-fed babies to 29 (6 mo), 17 (9 mo), and 10 (12 mo). Breast-feeding for 6 months or longer gave a 6.6-point advantage (95% confidence interval, -0.6, 13.8; P = 0.07 for the Bayley psychomotor developmental index (PDI) and 2.0 for the Bayley mental developmental index (MDI) (95% confidence interval, -3.2, 7.3; NS) compared with the 15 subjects breast-fed for fewer than 6 months. Among the milk lipid factors, the fat weight (mg/dL) at 6 months showed the highest association with the MDI (r = 0.55, P = 0.002). Thus, prolonged breast-feeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats contributing energy and/or affecting brain composition.

Aging↗

Long-chain polyunsaturated fatty acid concentrations in human hindmilk are constant throughout twelve months of lactation.

We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method. Fatty acids were analyzed by means of capillary gas chromatography. Comparisons were made with analysis of variance for repeated measures. Ten mothers completed the follow-up 12-month nursing period. We found that the total lipid content of hindmilk (mg/dL) rises more than 3-fold from the colostrum up to the 3rd month, and then more slowly up to the 12th month. Total saturated fatty acids progressively increase and total monounsaturated FA progressively decrease. Among long-chain polyunsaturated fatty acids, we found that the concentrations (mg/dL) of C20:4 and C22:6 remain stable from colostrum up to the 12th month of nursing, while their percentage levels are highest in colostrum and decrease afterwards in association with the increase in total fats. The C18:2n6 and C18:3n3 amounts progressively increase, following the trend of total fats. These data indicate that the secretion of arachidonic acid and docosahexaenoic acid during lactation remains constant, in spite of changes in total fat and in the linoleic acid and alpha-linolenic acid contents of milk.

Arachidonic Acid↗