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Biomedical subjects

M Giovannini

Publications and source records attributed to M Giovannini.

At least 73 records · Page 4Linked to original sources
PubMed2001

High-dose radiation therapy and neoadjuvant plus concomitant chemotherapy with 5-fluorouracil and cisplatin in patients with locally advanced squamous-cell anal canal cancer: final results of a phase II study.

PURPOSE: To analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced anal canal squamous-cell carcinoma (ACC). PATIENTS AND METHODS: Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52 T2, 14 T3, 13 T4, 18 N0, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (+/- inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one to two month gap (15-20 Gy). The median follow-up was 29 months. RESULTS: One patient died of a pulmonary embolism on day 4. All patients received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% after treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomy-free, relapse-free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% and 63%, respectively. CONCLUSIONS: Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.

Adult↗
PubMed2001

Effects of sildenafil on esophageal motility of normal subjects.

Sildenafil shows an intense and prolonged inhibitory effect on the smooth muscle cells of corpus cavernosum arterioles by blocking phosphodiesterase type 5 that inactivates the nitric oxide-stimulated cyclic guanosine monophosphate. We investigated if this inhibitory effect is also displayed on smooth muscle cells of the esophagus. In 16 normal subjects (9 men and 7 women, mean age 34 years, range 22-56) esophageal motility was recorded by means of a low-compliance manometric system with side holes for the esophageal body and a sleeve for the lower esophageal sphincter (LES). After a basal period of 60 min, a tablet of sildenafil 50-mg ground and dissolved in water was infused in the stomach in eight subjects (group A) and a placebo tablet in the other eight subjects (group B), randomly and in a double-blind manner; the recording continued for another 60 min. LES tone and postdeglutitive residual pressure, as well as amplitude, propagation velocity, and onset latency of contractions were measured each minute, the values averaged every 5 min, and the mean of the entire basal and postinfusion periods was calculated. The postinfusion values were compared with the basal values in each group and with the corresponding values of the other groups. The percent variations of postinfusion values with respect to basal values were also compared. Sildenafil induced a statistically significant decrease of LES tone, residual pressure, wave amplitude, and propagation velocity and a significant increase of onset latency of pressure waves in comparison with the values of the basal period and placebo. The inhibitory effect reached its maximum 10-15 min after the infusion and lasted about 1 hr. In conclusion, sildenafil markedly inhibits the motor activity of the esophageal musculature by decreasing LES pressure, wave amplitude, and propagation velocity and increasing the onset latency of pressure waves.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Breastfeeding duration, milk fat composition and developmental indices at 1 year of life among breastfed infants.

The associations of breastfeeding duration and milk fat composition with the developmental outcome at 1 year of age were measured within 44 infants exclusively breastfed for 3 months, out of 95 recruited at birth. Pooled breast milk (hindmilk) of the mothers was analysed at colostrum, 1, 3, 6, 9, and 12 months for total fat and fatty acid content. Infants were examined at 12 months by means of the Bayley test. There was a progressive reduction of the number of breastfed babies after the introduction of solids to 29 (6 months), 17 (9 months) and 10 (12 months). After adjusting for major confounders, infants breastfed for 6 months or longer showed a trend to have an advantage at the Bayley psychomotor developmental index compared to those breastfed >3 and <6 months (95% CI for difference: - 0.6, 13.8; P= 0.07) while the Bayley mental developmental index (MDI) was just 2.1 points higher. Among the milk fat components considered for each time-point, the total fat content at 6 months showed the strongest association with the MDI at 12 months (r=0.59, P=0.001). Prolonging breastfeeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats affecting brain composition.

Breast Feeding↗
PubMed2001

Biochemical effects of supplemented long-chain polyunsaturated fatty acids in hyperphenylalaninemia.

Hyperphenylalaninemic (HPA) children display low levels of long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), in circulating lipids and erythrocytes. We have investigated the effects on the blood fatty acid status and lipid picture of a balanced supplementation with LCPUFA in HPA children through a double-blind, placebo-controlled trial. A total of 20 well-controlled HPA, school-age children were randomized to receive through a 12-month trial fat capsules supplying either 26% fatty acid as LCPUFA (including 4.6%gamma -linolenic acid, 7.4% arachidonic acid, AA, 5.5% eicosapentaenoic acid and 8% DHA) or placebo (olive oil). The study supplementation was administered in order to provide 0.3-0.5% of the individual daily energy requirements as LCPUFA. Reference data were obtained from healthy children of comparable age. Among HPA children (whose DHA status was poor at baseline), those supplemented with LCPUFA showed an increase of around 100% in the baseline DHA levels in plasma phospholipids and erythrocytes. No changes of AA levels were observed. Blood lipid levels did not significantly change. A balanced supplementation with LCPUFA in treated HPA children may improve the DHA status without adversely affecting the AA status.

Adolescent↗
PubMed2001

Anal carcinoma: prognostic value of endorectal ultrasound (ERUS). Results of a prospective multicenter study.

BACKGROUND AND STUDY AIMS: The classification of anal carcinoma is based on the clinical examination and the estimation of the tumor height (Union Internationale Contre le Cancer (UICC) 1987 Classification). This classification has a direct therapeutic application since tumors which are designated T1 and T2 are generally treated by radiotherapy whereas T3, T4 or N+ lesions are treated by concomitant radiation and chemotherapy. The aim of this prospective multicenter study was to evaluate endorectal ultrasound (ERUS) and to define an ERUS-based classification. PATIENTS AND METHODS: Between January 1994 and May 1997, 146 patients (42 men and 104 women; mean age, 63) from eight different centers were studied prospectively. The ERUS classification incorporates disease of the anal canal and the perirectal lymph nodes, thus: usT1 describes involvement of the mucosa and submucosa with sparing of the internal sphincter; usT2, involvement of the internal sphincter with sparing of the external sphincter; usT3, involvement of the external sphincter; usT4, involvement of a pelvic organ; N0 describes no suspicious perirectal lymph nodes, and N+, perirectal lymph nodes fulfilling endosonographic criteria for malignancy (e.g. round, hypoechoic). Tumors classified as UICC T1-T2 (<4cm) N0 were treated by radiotherapy alone, whereas lesions with a UICC classification of T2 (> 4 cm), T3-T4, N0-N1-2-3 received combined radiochemotherapy. RESULTS: Data concerning the treatment and follow-up were available for 115/146 patients (78.7%). We compared the prognostic importance of the two classification schemes for treatment response and the rate of local relapse (chi-squared test). A significantly greater proportion of T1-T2N0 lesions classified by ERUS had a complete response to treatment than those classified by conventional UICC staging (94.5% vs. 80%, respectively; P = 0.008). The ERUS T and N stage were significant predictors of relapse (P=0.001 and P=0.03, respectively) whereas the corresponding clinical (UICC) stages were not (P = 0.4 and P = 0.5, respectively). Using a Cox model, usT stage was the only significant predictive factor for patient survival. CONCLUSION: This muticenter prospective study demonstrated the superiority of ERUS-based staging over traditional clinical staging in the prediction of important outcomes such as local tumor recurrence and patient survival.

Adult↗
PubMed2001

Endoscopic ultrasound-guided drainage of pancreatic pseudocysts or pancreatic abscesses using a therapeutic echo endoscope.

STUDY AIMS: The purpose of this study is to evaluate a new drainage technique for pancreatic pseudocysts or pancreatic abscesses entirely guided by endoscopic ultrasound (EUS) and using an interventional echo endoscope with a linear curved array transducer. PATIENTS AND METHODS: Between July 1996 and September 1999, EUS-guided drainage of a pancreatic pseudocyst or pancreatic abscess was carried out in 35 patients (26 men, 9 women; mean age 56.7, range 29-69). The mean size of the 35 pancreatic cysts was 7.8 cm (4-12 cm). Pancreatic pseudocysts were located in the head of the pancreas in two cases, in the body in six cases and in the tail in seven cases. On the other hand, the pancreatic abscesses were located in the tail of the pancreas in 17 cases and in the gastric wall in three cases. The EUS instrument used was the FG 38X endoscope manufactured by Pentax-Hitachi. RESULTS: No major complication occurred except in one case of a pneumoperitoneum, which was managed medically. Placement of the 7-F nasocystic drain was successful in 18/20 cases of pancreatic abscess. Surgery was performed in the two other patients. Concerning the pancreatic pseudocysts, placement of an 8.5-French stent was successful in 10 patients and of a nasopancreatic drain in five patients. In one case, only a puncture-aspiration was performed. One recurrence among the 15 pancreatic pseudocysts and two relapses of the 18 pancreatic abscesses have been observed, over a mean follow-up of 27 months (6-48 months). EUS-guided drainage was successful in 31/35 patients (88.5%); only four patients with pancreatic abscesses underwent surgery. No bleeding occurred during the time of this study. CONCLUSION: Internal drainage of pancreatic pseudocysts and abscesses exclusively performed with an echo endoscope is a safe and efficient method which should be evaluated further in larger studies.

Abdominal Abscess↗
PubMed2001

Endoscopic ultrasound-guided bilioduodenal anastomosis: a new technique for biliary drainage.

Endoscopic biliary stenting is the most common method of treating obstructive jaundice. We present a new technique of biliary drainage using endoscopic ultrasound (EUS) and EUS-guided puncture of the common bile duct (CBD). A 56-year-old man with obstructive jaundice was referred for EUS and endoscopic retrograde cholangiopancreatography (ERCP) because a computed tomography (CT) scan had shown a pancreatic mass in the head of the pancreas and a dilated CBD. The patient was enrolled in a preoperative chemoradiotherapy protocol and biliary stenting was required. Deep cannulation was not obtained even after a precut and the procedure was stopped. Using a therapeutic EUS scope (FG 38X Pentax), the CBD was punctured with a 5-F needle-knife under EUS guidance and a cholangiogram was obtained. A 0.35-inch guide wire was introduced into the CBD. The EUS scope was removed and a duodenoscope was introduced, allowing the placement through the duodenum of a 10-F plastic stent. The CBD was drained properly. No complication occurred.

Adenocarcinoma↗
PubMed2001

Cognitive and visual development: influence of differences in breast and formula fed infants.

Several recent studies document a beneficial effect of breast-feeding on later neurodevelopmental outcomes. The mechanisms involved are still in need of elucidation, but evidence is accruing that the fatty acid (FA) composition of human milk plays a role. The composition of body fats, from circulating erythrocyte lipids to brain phospholipids, is linked in infants to the early feeding mode and which FA predominates among circulating lipids influences visual and neurodevelopmental performance test scores. In these studies, greater differences were found between breast-fed and standard formula-fed infants, the latter showing low tissue long-chain polyunsaturated fatty acids (LCPUFA: arachidonic acid, AA, 20:4n-6; eicosapentaenoic acid, EPA, 20:5n-3; docosahexaenoic acid, DHA, 22:6n-3) accretion and lower visual and neurodevelopmental test scores. Human milk contains LCPUFA, while most available formulas, especially those intended for full-term infants, do not. With the progressive introduction of solid foods, the question arises whether a specific or "ideal" dietary lipid mixture can be found to meet growth requirements and ensure a lipid balance adequate for the early and effective preventive purposes. These complementary aspects are challenges for the paediatric nutrition researcher today.

Breast Feeding↗
PubMed2001

MSH2 and MLH1 immunodetection and the prognosis of colon cancer.

MSH2 and MLH1 are proteins involved in DNA reparation. They are mutated in some forms of colon cancer, i.e. hereditary non-polyposis carcinomas and a subset of sporadic carcinomas. We have studied the expression of MSH2 and MLH1 in a retrospective series of 225 colorectal carcinomas by immunohistochemistry. The results were compared to molecular tests of microsatellite instability using amplification by PCR of BAT-25 and BAT-26 repeated sequences and to histoclinical data. Positivity of both proteins was never associated with MSI phenotype. MSH2 and/or MLH1 negative tumors were frequently tumors of the proximal colon; in this subpopulation or proximal tumors, MSH2 and/or MLH1 negativity was associated with a longer disease-free survival.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.

Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is inactivated. We report that conditional homozygous Nf2 knockout mice with Cre-mediated excision of Nf2 exon 2 in Schwann cells showed characteristics of neurofibromatosis type 2. These included schwannomas, Schwann cell hyperplasia, cataract, and osseous metaplasia. Thus, the tumor suppressor function of Nf2, here revealed in murine Schwann cells, was concealed in hemizygous Nf2 mice because of insufficient rate of second allele inactivation in this cell compartment. The finding of this conserved function documents the relevance of the present approach to model the human disease.

Alleles↗
PubMed2000

TEL-JAK2 transgenic mice develop T-cell leukemia.

We previously reported a fusion between TEL and JAK2 in a t(9;12)(p24;p13) chromosomal translocation in childhood acute T-cell leukemia. This fusion gene encodes a TEL-JAK2 chimeric protein in which the 336 amino-terminal residues of TEL, including its specific self-association domain, are fused to the kinase domain of JAK2. TEL-JAK2 exhibits constitutive activation of its tyrosine kinase activity which, in turn, confers growth factor-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line. To elucidate the properties of TEL-JAK2 in primary cells and to create an animal model for TEL-JAK2-induced leukemia, we generated transgenic mice in which the TEL-JAK2 complementary DNA was placed under the transcriptional control of the EmuSRalpha enhancer/promoter. TEL-JAK2 founder mice and their transgenic progeny developed fatal leukemia at 4 to 22 weeks of age. Selective amplification of CD8-positive T cells was observed in blood, lymph nodes, thymus, spleen, and bone marrow. Expression of a tyrosine-phosphorylated TEL-JAK2 protein and activation of STAT1 and STAT5 (signal transducer and activator of transcription) were detected in leukemic tissues. TEL-JAK2 diseased mice also displayed invasion of nonhematopoietic organs, including liver, brain, lung, and kidney, by leukemic T cells. Leukemic organs of founder and transgenic progeny contained a monoclonal/oligoclonal T-cell population as analyzed by the rearrangement of the TCRbeta locus. Transplantation of TEL-JAK2 leukemic cells in nude mice confirmed their invasive nature. We conclude that the TEL-JAK2 fusion is an oncogene in vivo and that its expression in lymphoid cells results in the preferential expansion of CD8-positive T cells. (Blood. 2000;95:3891-3899)

Animals↗
PubMed2000

[Management of pain in pancreatic cancer].

Pain remains an indicator of progression of cancer of the pancreas. Regular pain evaluation combined with early analgesic treatment improves the duration and quality of life. New modes of morphine administration and specific chemotherapy can improve this management. Neurolysis is more effective in the case of recent pain, previously controlled by anti-inflammatory drugs. The endoscopic ultrasound (EUS)-guided technique allows celiac block during EUS examination for local staging. Early introduction of palliative surgery and analgesic procedures can reduce the morbidity and mortality of these procedures. A graduated multidisciplinary pain management program allows optimal pain control.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Adolescence: macronutrient needs.

Dietary needs during adolescence lack specific definitions, and most evidence is derived from indirect indications. The data on dietary needs for energy and proteins are mainly extrapolated from subjects in other age-classes. Lipids and carbohydrates are being progressively considered for preventive purposes since the qualitative distribution of saturated and unsaturated fats and slowly and rapidly absorbed carbohydrates, respectively, seems to be associated with metabolic index predictors of degenerative disorders in later stages of life. The recent results of multicentric autoptic studies in young people from the US indicate that the lipoprotein status of the second decade of life is associated with the first raised arterial lesions in the third decade. The evidence of these links needs further confirmation from ongoing surveys. We must recognize that adolescence is a critical period of life, and food fads may deeply change the dietary habits acquired within the familiar group. As nutritionists, we may suggest that all adolescents should be supplied with nutritional support in terms of education, maybe at school, to improve their knowledge of nutrition.

Adolescent↗
PubMed2000

Early macronutrient intake and overweight at five years of age.

OBJECTIVE: To examine the influence of the macronutrient intake in early life on the development of overweight in children. DESIGN AND SUBJECTS: An ongoing longitudinal study including 147 randomized healthy children followed up from birth. MEASUREMENTS: Anthropometric parameters were measured at birth, 1 and 5 y of age. Dietary habits at the age of 1 and 5 were assessed by age-adjusted food-frequency questionnaires and 24 h recalls. Parents' body mass index (BMI) was also recorded. RESULTS: Parental overweight was observed for 51% children. The prevalence of overweight at the age of 5 y was higher in children with than without parental overweight (37.3% vs 8.3%, P<0.0001). Five-year old overweight children had a higher percentage intake of proteins at the age of 1 y than non overweight children (22% vs 20%, P=0.024) and lower intake of carbohydrates (44% vs 47%, P=0.031). Multiple logistic analysis confirmed that protein intake at 1 y of age was associated with overweight at 5 y (P=0.05). In children born from overweight mothers, prevalence of overweight at the age of 5 y tended to be higher in bottle-fed than in breast-fed ones (62.5% vs 23.3%, P=0.08). CONCLUSION: Parental overweight is a major risk factor for childhood overweight in the first years of life, but an early high protein intake may also influence the development of adiposity.

Body Mass Index↗