To demonstrate that the lipid volume fraction in liver steatosis can be accurately estimated with in vivo hydrogen-1 magnetic resonance (MR) spectroscopy, the authors developed a calibration procedure based on in vitro MR spectroscopy of lipid extracts from steatotic liver specimens. The lipid volume fractions determined with the calibration procedure were compared with the results of histomorphometry and with calibrated computed tomographic (CT) data. The volume fraction of fat determined with MR spectroscopy was in good agreement with the CT results, whereas histomorphometry underestimated the amount of hepatic fat. The results indicate that determination of the fat volume fraction in steatotic liver can be achieved noninvasively with MR spectroscopy.

Adult↗

PubMedDate not supplied

Quantitative 31P MRS of the normal adult human brain. Assessment of interindividual differences and ageing effects.

The characteristics of the 31P MR spectra from a large central volume in the brain of 47 healthy adults (aged 25-85 years) were assessed. Spectral parameters were estimated by means of a time-domain fitting technique. Statistical uncertainties of the estimates were determined by means of the Cramer-Rao theory and minimized by introducing a priori knowledge into the fitting procedure. Age-dependency of the spectral parameters was assessed by means of linear regression. Significant differences between individuals were established for some parameters. A significant age-dependency (p < or = 0.001) of ca 20% over the age range considered was found for the intensity of the phosphocreatine resonance line.

Adenosine Triphosphate↗

PubMedDate not supplied

Fasting and post-prandial glycemia and their correlation with glycated hemoglobin in Type 2 diabetes.

OBJECTIVE: The relative contribution of fasting and post-prandial glucose to glycated hemoglobin (HbA1c) is controversial. In the present study, we assessed the relationship with HbA1c of fasting and post-prandial glucose measured in a more naturalistic setting, through home glucose self-monitoring or with a continuous glucose monitoring system (CGM). MATERIALS AND METHODS: A consecutive series of 300 patients with Type 2 diabetes were enrolled in the study, provided that they performed blood glucose self-monitoring. HbA1c and fasting plasma glucose (FPG) were measured at enrolment. RESULTS: Both fasting plasma and capillary glucose showed a significant correlation with HbA1c (r=0.66 and 0.61, respectively; p<0.001). When home glucose monitoring was considered, both mean fasting and post-prandial glucose showed a significant correlation with HbA1c (r=0.71 and 0.73, respectively). In patients in the lower tertile of body mass index (BMI), HbA1c showed a significant correlation at multivariate analysis with post-prandial glucose, but not with fasting glucose. In patients with HbA1c >7%, both fasting and post-prandial glucose showed a significant correlation, after adjustment for age and BMI, with HbA1c (both p<0.01); conversely, in those with HbA1c < or =7%, such a correlation could be observed for fasting (p<0.01), but not for post-prandial glucose. CONCLUSION: In conclusion, both fasting and post-prandial glucose contribute to the determination of HbA1c . Home glucose self-monitoring appears to provide a more accurate assessment of metabolic control than a single plasma glucose measurement in experimental conditions. Fasting glucose could provide a greater contribution to HbA1c in patients with lower HbA1c, while post-prandial glucose seems to play a major role in leaner Type 2 diabetic subjects.

Aged↗

PubMedDate not supplied

Sequential adjuvant hormone therapy in postmenopausal breast cancer: rationale and clinical results.

For the past 15 years tamoxifen has been the standard adjuvant hormone therapy for women with early-stage breast cancer and estrogen receptor (ER)-positive tumors, irrespective of nodal status and other clinicopathological parameters. Recent studies provided evidence that the optimal duration of tamoxifen treatment is 5 years. Based on the positive clinical results obtained with the administration of aromatase inhibitors (AIs) in the metastatic setting, several controlled clinical trials have evaluated the efficacy and side effects of AIs versus standard tamoxifen also as adjuvant therapy in postmenopausal breast cancer patients. The results of the above studies, suggest a therapeutic advantage of AIs over tamoxifen with regard to relapse-free survival and the risk of metachronous contralateral breast cancer. We review the rationale and the available clinical data on initial or sequential hormone treatment with AIs and we propose a novel scenario for possible therapeutic strategies based on the clinicopathological characteristics of the patients and on the biology of each single tumor.

Antineoplastic Agents, Hormonal↗

PubMedDate not supplied

Bolus and infusional 5-fluorouracil combined with cisplatin in advanced gastric cancer.

5-Fluorouracil (5-FU) is the main drug used in the treatment of advanced gastric cancer. Combination chemotherapy is not always superior to 5-FU alone, especially when biomodulators are also administered. In an attempt to exploit all the cytotoxic mechanisms of 5-FU, we carried out a pilot study with a double route of administration of 5-FU (intravenous bolus and continuous infusion) and a multiple modulation of 5-FU by methotrexate (MTX), 6S-leucovorin (6S-LV) and cisplatin (CDDP). A group of 30 patients affected by advanced gastric cancer was treated with MTX 50 mg/m2 and 5-FU 400 mg/m2 as an i.v. bolus on day 1, followed by a 5 day i. v. continuous infusion of 5-FU 600 mg/m2/day and 6S-LV 100 mg/m2/day; on day 3 CDDP 100 mg/m2 was also administered. The regimen was repeated every 4 weeks. Six partial responses (20+/-14. 3%), 12 stable diseases (40+/-17.5%) and 12 progression (40+/-17.5%) were observed in an intent-to-treat analysis. Median survival was 7 months. All responding patients had performance status 0-1. Grade 3-4 toxicity was mainly gastrointestinal, but grade 3-4 anemia and leucopenia were also recorded. The schedule has low activity. The use of different modulators and way of administration of 5-FU does not provide advantages in advanced gastric cancer.

Adult↗

PubMedDate not supplied

Stability of ranitidine tablets subjected to stress and environmental conditions, by HPLC.

High Performance Liquid Chromatographic (HPLC) method was applied in this study to comparatively evaluate the stability of tablets in their original package which 150 mg of Ranitidine from six different pharmaceutical laboratories in the market, according to ICH conditions for accelerated testing: 40 degrees C, 75% RH with and without light for six months. The stability at environmental conditions was evaluated for a twelve-month period, with and without light, with the same purpose. Ranitidine is widely used to treat peptic ulcer diseases. Ranitidine is susceptible to degradation under the influence of light, humidity and temperature. The chromatographic conditions were: RP-18 column of 250 mm yen 4 mm ID and a particle size of 5 mm; mobile phase of Acetonitrile-Ammonium acetate solution (0.2 M) (70:30; v/v) (pH*6) adjusted with glacial acetic acid; flow rate of 1 ml min-1; 25 degrees C of temperature; detection at 322 nm; injection volume of 20 ml, using height peak as the integration parameter. The results obtained at six months indicate that the stability of Ranitidine depends on the correct formulation and the primary container. The remaining content of Ranitidine, dissolved percentage in vitro and total impurity percentage were determined by HPLC. Organoleptic characteristics were visually examined. The proposed analytical method was validated and linearity, precision and selectivity were determined. Degradation products were detected.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Antiviral Agents↗

PubMedDate not supplied

[Clinical magnetic resonance spectroscopy. The state of the art].

Magnetic resonance spectroscopy is a noninvasive technique which allows the study of the chemical composition of tissue. In the first part of this paper the authors describe the physical principles and the technical features of spectroscopy, including spectral acquisition, localization techniques and peak quantification. The second part of the paper regards the evaluation of the biological significance of the peaks observed in the most frequently studied spectra (31P and 1H). The third part concerns the clinical feasibility of magnetic resonance spectroscopy: in order to employ spectroscopy in the clinical practice, this technique should be able to fulfill such requirements as tissue characterization, metabolic quantification, therapy follow-up, biochemical understanding of the physiopathologic phenomena and pH evaluation. The fourth and last part of this paper deals with the clinical applications of spectroscopy. The authors consider the results of other research groups in the spectroscopic evaluation of the striate muscle, the central nervous system, heart, liver and some other organs. Then they describe some preliminary personal results in cerebral spectroscopy (41 healthy subjects studied with 31P and 5 with 1H) and liver spectroscopy (19 healthy subjects studied with 31P and 9 healthy subjects and 9 patients with liver steatosis studied with 1H). The authors conclude that the problem of the potential clinical application of spectroscopy is still open. So far the use of this technique is limited to research centers, which should point out the clinical role of spectroscopy.

Humans↗

PubMedDate not supplied

[Clinical experiences with the use of gentamicin in newborn and premature infants].

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Bronchopneumonia↗