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Biomedical subjects

M Giovannini

Publications and source records attributed to M Giovannini.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency.

The oral loading test with tetrahydrobiopterin (BH(4)) is used to discriminate between variants of hyperphenylalaninaemia and to detect BH(4)-responsive patients. The outcome of the loading test depends on the genotype, dosage of BH(4), and BH(4) pharmacokinetics. A total of 71 patients with hyperphenylalaninaemia (mild to classic) were challenged with BH(4) (20 mg/kg) according to different protocols (1 x 20 mg or 2 x 20 mg) and blood BH(4) concentrations were measured in dried blood spots at different time points (T(0), T(2), T(4), T(8), T(12), T(24), T(32) and T(48 h)). Maximal BH(4) concentrations (median 22.69 nmol/g Hb) were measured 4 h after BH(4) administration in 63 out of 71 patients. Eight patients presented with maximal BH(4) concentrations approximately 44% higher at 8 h than at 4 h. After 24 h, BH(4) blood concentrations dropped to 11% of maximal values. This profile was similar using different protocols. The following pharmacokinetic parameters were calculated for BH(4) in blood: t (max) = 4 h, AUC (T(0-32)) = 370 nmol x h/g Hb, and t (1/2) for absorption (1.1 h), distribution (2.5 h), and elimination (46.0 h) phases. Maximal BH(4) blood concentrations were not significantly lower in non-responders and there was no correlation between blood concentrations and responsiveness. Of mild PKU patients, 97% responded to BH(4) administration, while one was found to be a non-responder. Only 10/19 patients (53%) with Phe concentrations of 600-1200 mumol/L responded to BH(4) administration, and of the patients with the severe classical phenotype (blood Phe > 1200 mumol/L) only 4 out of 17 patient responded. An additional 36 patients with mild hyperphenylalaninaemia (HPA) who underwent the combined loading test with Phe+BH(4) were all responders. Slow responders and non-responders were found in all groups of HPA.

Administration, Oral↗
PubMed2006

Positive cross correlations in a normal-conducting fermionic beam splitter.

We investigate a beam-splitter experiment implemented in a normal-conducting fermionic electron gas in the quantum Hall regime. The cross correlations between the current fluctuations in the two exit leads of the three terminal device are found to be negative, zero, or even positive, depending on the scattering mechanism within the device. Reversal of the cross correlation sign occurs due to interaction between different edge states and does not reflect the statistics of the fermionic particles which "antibunch."

Journal Article↗
PubMed2006

Anorectal ultrasound for neoplastic and inflammatory lesions.

Accurate staging of rectal and anal carcinoma is crucial for planning surgery and indicating adjuvant therapy. Although, computed tomography and magnetic resonance imaging are very sensitive in detecting metastatic disease, the local staging of rectal cancer with these techniques has been disappointing. Endorectal ultrasound (ERUS) and anal endosonography (AE) remain the most accurate methods for staging rectal and anal cancer. Anal endosonography is also of value in evaluating perianal sepsis: it can assist the surgeon in planning the surgical strategy by delineating the anatomy of fistula tracts, and can aid in puncturing abscesses in the operating room. Continued research and development has made the instrumentation for ERUS and AE more accurate and user-friendly. New techniques that have contributed significantly to the evolution of ERUS include three-dimensional ERUS, high-frequency miniprobes, transrectal ultrasound-guided biopsy techniques and hydrogen peroxide-enhanced endosonography. Further improvements can be expected from contrast enhancement with microbubbles and colour Doppler imaging. In this new millennium, new developments in ERUS and anal endosonography, such as tri-dimensional ERUS and anal endosonography and radial electronic probing, widen the role of ERUS in the staging of rectal and anal carcinoma, as well as for perianal inflammatory conditions.

Endosonography↗
PubMed2006

Three-dimensional endorectal ultrasound using a new freehand software program: results in 35 patients with rectal cancer.

BACKGROUND AND STUDY AIMS: This paper describes experience in the staging of rectal cancer using a new software program for three-dimensional endoscopic ultrasonography (EUS) that works without electromagnetic sensors and can be used even with electronic radial or linear rectal probes. MATERIALS AND METHODS: From May 2003 to March 2004, 35 three-dimensional endorectal ultrasound (ERUS) examinations were carried out using this program. The indication for ERUS was local staging of rectal cancer in all cases. The three-dimensional software imaging program forms part of a new ultrasound scanning system (Hitachi 6500 or 8000) and allows reconstruction of the two-dimensional EUS images in six different scans. RESULTS: Thirty-five rectal cancers were assessed using two-dimensional and three-dimensional EUS. Using two-dimensional imaging, it was not possible to assess precisely the degree of involvement of the mesorectum (more or less than 50%). No differences were evident with three-dimensional EUS for superficial tumors (T1 and T2N0), but in six of 15 patients classified as having T3N0 lesions, three-dimensional EUS revealed malignant lymph nodes, a finding that was confirmed surgically in five of the six cases. Three-dimensional EUS also made it possible to assess the degree of infiltration of the mesorectum precisely in all cases, demonstrating complete invasion of the mesorectum in eight cases. These findings were confirmed in all cases by the surgical data. Two-dimensional EUS correctly assessed 25 of the 35 rectal tumors (71.4%) in relation to the T and N classifications, and three-dimensional EUS increased this figure to 31 correct evaluations out of 35 (88.6%). CONCLUSION: Three-dimensional ERUS is easy to carry out using this new software program. There is no need for an external sensor mounted at the tip of the probe, and manipulation of the rectal probe is facilitated. Three-dimensional ERUS can be carried out using linear and radial electronic probes with the same ultrasound equipment. Three-dimensional ERUS allows more precise staging of lesions and better definition of the mesorectal margins, and this has a direct impact on therapeutic decision-making in patients with rectal cancer.

Endosonography↗
PubMed2006

Endoscopic mucosal resection for advanced sessile adenoma and early-stage colorectal carcinoma.

BACKGROUND AND STUDY AIMS: The aim of this study was to evaluate the efficacy and outcomes of treatment by endoscopic mucosal resection (EMR) of patients with high-grade dysplasia (HGD) or carcinoma. PATIENTS AND METHODS: Between January 1995 and January 2002, 50 patients (35 men, 15 women) were treated by EMR for 52 sessile polyps. The median size of the polyps was 27.5 mm (range 10-60). The "lift and cut" EMR technique was used. If the lesion was poorly differentiated or infiltrated the muscularis mucosae to more than 1000 microm, the patient was referred for colectomy. In the other cases, follow-up was proposed. RESULTS: Complications occurred in 9.6 % of cases and were always treated conservatively. The rate of endoscopically complete resection was judged to be 98.1 %. Argon plasma coagulation was applied to the margins of the lesion in 21.6 % of cases. Histological examination showed 38 HGDs and 14 carcinomas. Seven patients had a lesion reaching the deep or lateral margin; four were referred for surgery; two patients for whom surgery would have been high risk were followed up, and both developed local recurrence; and one patient was followed up, without recurrence, because infiltration was less than 1000 microm. A total of 43 patients were followed up after complete excision. Two patients died during follow-up; neither death could be reliably attributed to colorectal carcinoma. Seven patients were lost during the follow-up. For 34 patients, information from a mean follow-up of 17.3 months (6 - 57) was available and recurrence was observed in five cases (15 %). CONCLUSIONS: EMR appears to be a safe and efficient treatment of HGD and early colorectal cancer. However, correct analysis of submucosal infiltration is essential to assess the completeness of the resection.

Adenoma↗
PubMed2006

Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients.

BACKGROUND AND STUDY AIMS: It is well known that some diseases, such as cancer, lead to changes in the hardness of tissue. Sonoelastography, a technique that allows the elasticity of tissue to be assessed during ultrasound examination, provides the ultrasonographer with important additional information that can be used for diagnosis. The aim of this study was to evaluate the ability of endoscopic ultrasound elastography to differentiate between benign and malignant pancreatic masses and lymph nodes. PATIENTS AND METHODS: During a 12-month period, 49 patients underwent endoscopic ultrasound (EUS) examinations with elastography, conducted by a single endoscopist. Twenty-four patients underwent evaluation of a pancreatic mass (mean diameter 24.7 +/- 11.1 mm) and 25 underwent evaluation of 31 lymph nodes. The mean diameter of the lymph nodes was 19.7 +/- 8.6 mm, and they were found in the cervical area (n = 3), mediastinum (n = 17), celiac arterial trunk region (n = 5), and aortocaval region (n = 6). RESULTS: The sonoelastography images of pancreatic masses were interpreted as benign in four cases and malignant in 20. The sensitivity and specificity of sonoelastography in the diagnosis of malignant lesions were 100% and 67%, respectively. The sonoelastography images of the lymph nodes were interpreted as showing malignancy in 22 cases, benign conditions in seven, and indeterminate status in two. The sensitivity and specificity of sonoelastography for evaluating malignant lymph-node invasion were 100% and 50%, respectively. CONCLUSIONS: EUS elastography is potentially capable of further defining the tissue characteristics of benign and malignant lesions but specifity has to be improved. It can be used to guide biopsy sampling for diagnosis.

Adolescent↗
PubMed2006

Practice parameters for sublingual immunotherapy.

The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, meta-analysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre co-seasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient's tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).

Administration, Sublingual↗
PubMed2005

Obstructive sleep apnoea is improved by a prolonged treatment of gastrooesophageal reflux with omeprazole.

BACKGROUND: Obstructive sleep apnoea has been demonstrated to induce gastrooesophageal reflux through highly negative intrathoracic pressure during the attacks. However, we believe that gastrooesophageal reflux on its part may favour or aggravate the apnoea attacks. AIMS: We investigated whether the treatment of gastrooesophageal reflux with omeprazole is able to decrease apnoea attacks. PATIENTS AND METHODS: Twenty patients (mean age 55.4 years, range 49-73 years; 17 males) with confirmed obstructive sleep apnoea at overnight polysomnography and pathological gastrooesophageal reflux at ambulatory 24-h oesophageal pHmetry were asked to note in a diary the occurrence of apnoea attacks for a basal period of 4 weeks. Subsequently, the patients were randomly and in a double-blind manner treated with omeprazole 20mg (10 patients, group A) or placebo (10 patients, group B) by giving 1 cp 30 min before breakfast and 1 cp 30 min before dinner for another 6 weeks with a diary documentation. The results were averaged weekly and over the entire treatment duration and a statistical comparison was made between the groups and within each group before and after treatment. RESULTS: The mean weekly frequency of apnoea attacks of group A during the entire period of treatment with omeprazole was significantly decreased with respect to the basal period and was significantly lower than that of group B. The weekly frequency of apnoea attacks in group A started to be significantly lower from the third week than the corresponding values of both group B and the basal period, reaching a decrease of about 73% in the sixth week. CONCLUSION: The occurrence of apnoea attacks progressively decreased during the treatment of gastrooesophageal reflux with omeprazole. This fact suggests that gastrooesophageal reflux may play a role in triggering and/or worsening obstructive sleep apnoea.

Aged↗
PubMed2005

[Major hepatectomy for metastasis of colorectal cancer improves survival in the elderly].

OBJECTIVE: Assessing impact of major liver resection (LR) for hepatic metastasis of colorectal cancer (HMCC) on post operative courses and long term survival in the elderly. PATIENTS AND METHOD: Thirty-three consecutive patients aged over 70 years-old were treated in our institution for up to 3 resectable metachronous HMCC. Fifteen patients had major LR (9 right hepatectomy, 3 extended right hepatectomy, 3 left hepatectomy) without pre or postoperative chemotherapy (group 1) and 18 patients were exclusively treated by chemotherapy (group 2) because of high ASA score (ASA 3) or patients refusal. RESULTS: No patients died of another cause that colorectal cancer disease during observation time. All patients of group 2 died during observation time. Post operative mortality and morbidity of group 1 were respectively 0% and 33%. Survival at 1 and 2 years of group 1-2 were respectively 73-50% (P=0,04) and 47-15% (P=0,05). Median survival of group 1 and 2 were respectively 22 and 12 months (P=0,03). CONCLUSIONS: Major LR for HMCC could be proposed regardless the age. High ASA score, multiple (more than 4) metastasis location, evolutive disease could justify an exclusive medical approach.

Age Factors↗
PubMed2005

How much protein is safe?

BACKGROUND: Since breastfeeding and human milk seem to prevent, while high dietary proteins in the first 2 y of life seem to promote, later overweight, questions have been raised on the safe levels of proteins in the early years. How much protein (as a percentage of total calorie intake) is safe? METHODS: Revision of available data on the protein content of human milk, protein intake in the first 2 y of life and their association with body mass development. RESULTS: We should move from the figure of 7-8% in the 4-month exclusively breastfed infants up to the maximum acceptable levels of 14% in 12-24-month-old infants. When protein supply represents less than 6% and energy is limited, fully breastfed infants are likely to enter a status of negative nutrient balance. Over the limit of 14% energy from proteins in the 6-24 months period, some mechanisms may begin to operate, leading young children towards an early adiposity rebound and overweight development, beyond any genetic predisposition. Preliminary data seem to indicate a causal role for whole cow's milk proteins. CONCLUSION: We suggest maintaining breastfeeding as long as possible, and, in case human milk is insufficient, to introduce infant formulas, appropriate for age, up to 18-24 months, in order to keep protein intakes in the safe range of 8-12% within a diet adequate in energy and balanced as far as macronutrients.

Animals↗
PubMed2005

Dietary glycemic load and macronutrient intake in healthy Italian children.

The objective is of this study is to examine the relationship of dietary glycemic load (GL) and overall glycemic index (OGI) with macronutrients intake, body mass index (BMI) and insulin sensitivity in healthy children. The subjects comprised of 105 healthy non-obese eight-years old children, 60 boys and 45 girls. A Food Frequency Questionnaire (FFQ) evaluating dietary habits, GL and OGI. Insulin sensitivity was evaluated by the homeostatic model assessment (HOMA). GL was positively associated with dietary total (correlation coefficient, r=0.57) and starch (r=0.67) carbohydrates, daily consumption of pasta and white bread, cooked potatoes, bakery products and cookies, and negatively with dietary fats (r=-0.52). OGI was positively associated with daily consumption of white bread and cookies, and negatively associated with soluble carbohydrates (r=-0.35), and consumption of fibres, proteins, fruit, legumes and carrots. No significant association was found of GL or OGI with BMI or insulin sensitivity. In healthy children, GL and OGI may represent a useful indicator of quality of diet.

Child↗
PubMed2005

Comparison of allergen immunotherapy and drug treatment in seasonal rhinoconjunctivitis: a 3-years study.

Drug treatment and specific immunotherapy (SIT) are both effective in seasonal rhinoconjunctivitis, but the former acts only on allergic symptoms while the latter modifies the natural history of the disease. Only a few studies compared the clinical efficacy of the two treatments with contrasting results. We planned a study to compare the efficacy of SIT (15 patients) and drug treatment (15 patients) in moderate to severe seasonal rhinoconjunctivitis caused by sensitization to grass pollen. SIT was performed by a 5-grass extract standardized in IR and absorbed onto calcium phosphate (Phostal, Stallergénes, Antony, France) using the conventional build-up phase in 12 weeks and a maintenance treatment with monthly injection for three years. Drug treatment was done with cetirizine as antihistamine, mometasone furoate as nasal topical steroid, and levocabastine eyedrops. All patients registered during the pollen season their symptoms and drug consumption. After one year 12 of 15 patients treated with SIT had less symptoms and drug consumption in respect to baseline compared to none in drug treated group (p = 0.021) and after three years 15 of 15 were improved in group A compared to one of 15 in group B (p = 0.008). These findings indicate an higher efficacy of SIT in patients with seasonal rhinitis not only in the long term but also in the first year of treatment.

Administration, Intranasal↗
PubMed2004

Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas.

Although inappropriate activation of the Wnt/beta-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apc(lox/lox), in which exon 14 of the tumor-suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences. i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity [10(9) plaque-forming units (pfu) per mouse] inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. beta-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of beta-catenin in the hepatocytes and by the induction of beta-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 x 10(9) pfu per mouse), compatible with both survival and persistence of beta-catenin-activated cells. In these conditions, 67% of mice developed HCC. beta-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/beta-catenin pathway by invalidation of Apc is required for liver tumorigenesis.

Animals↗
PubMed2004

[Clinical practice guidelines: 2004 Standards, Options and Recommendations for the management of patient with adenocarcinoma of the stomach--radiotherapy].

CONTEXT: "The Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French regional cancer centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To elaborate clinical practice guidelines for patients with stomach adenocarcinoma. These recommendations cover the diagnosis, treatment and follow-up of these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. The Standards, Options and Recommendations are thus based on the best available evidence and expert agreement. RESULTS: Adjuvant radiation therapy alone is not a standard treatment for patients with stomach adenocarcinoma. Adjuvant concomitant chemoradiotherapy is not a standard treatment for patients with stage II or III stomach adenocarcinoma R0, with Dl or D2 lymphadenectomy who have undergone surgery. Following surgical resection, adjuvant concomitant chemoradiotherapy should be proposed to patients without denutrition with a lymphadenectomy < Dl (fewer than 15 lymph nodes examined) and those with T3 and/or N+ tumours following the protocol used in the MacDonald trials (SWOG-9008) (Level of evidence B1). Adjuvant concomitant chemoradiotherapy can be administered to patients without denutrition with DI or D2 lymphadenectomy and with involvement of regional lymph nodes (N2 or N3).

Adenocarcinoma↗