Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.     

Giant aneurysm of the pericallosal artery

A rare case of a giant aneurysm of the pericallosal artery, evaluated by computed tomography, magnetic resonance imaging, and angiography, is reported, and the other 7 cases in the literature are reviewed. Giant aneurysms are exceptional in the distal segments of the anterior cerebral arteries, and may simulate a callosal tumor or hematoma on computed tomographic scan. The clinical, radiological, surgical, and pathological findings of giant aneurysms of this location are discussed and the other reported cases are analyzed. The role of magnetic resonance imaging in diagnosing and characterizing giant aneurysms is stressed.     

Nutritional status of the elderly in Naples

Nutritional status (anthropometry, food habits, thiamin and riboflavin status) has been evaluated in 136 (70 males and 66 females) free living healthy elderly individuals (age range 65-69 yrs) from the district of San Carlo Arena that can be considered representative of the sociocultural and economic level of the city of Naples. By assuming as reference values those of middle aged individuals, 50 percent of elderly men and 85 percent of elderly women showed different degree of excess body fat. As far as food habits are concerned legumes, vegetables and fruit daily intake was quite high whilst alcohol consumption was low. Furthermore milk and eggs intake was low and infrequent. Although prevalence of excess body weight was high, total daily energy intake was found to be equal or slightly above dietary recommendations for the elderly. Diet composition showed a high protein intake whilst CHO and fat intake was slightly below recommendations. Micronutrients' intake was insufficient for calcium in 10 percent of both males and females and for iron in 20 percent of men and 40 percent of women. Niacin intake was low in about 50 percent of both men and women. Thiamin nutritional status was found low in 20 percent of men and women and riboflavin status in 40 percent of men and 20 percent of women. In conclusion obesity and overweight are very frequent in an urbanized sample of free living healthy elderly individuals of Naples. On the other hand serum calcium and iron and some vitamin deficiency is not uncommon. The composition of the diet seems to be also poor in some micronutrients.     

Inter- and intra-individual variability in food intake of elderly people in Perugia (Italy).

It has been shown that each individual has a considerable day-to-day variation (intra-individual variation) in his or her level of food consumption. A large intra-individual variation has adverse effects on the reliability of research studies. The effect of the intra-individual variation can be minimized by taking food intake records over several days. An increase in the number of days entails higher costs, and this could limit the practicability of the study. In the recent literature on the methodology of dietary surveys, there is a growing interest in the estimation of the number of days required to conduct a reliable dietary survey. Recent developments in statistical theory allow the problem of large intra-individual variability to be overcome. These new statistical techniques require knowledge of the intra- and inter-individual variability and the appropriate adjustment of the statistical results. The aim of the present study was to evaluate the number of days of recorded intake required to obtain an estimate of the components of variance (the inter-individual and the intra-individual variability) focusing on foods rather than nutrients.     

Preliminary investigation of respiratory self-gating for free-breathing segmented cine MRI.

Segmented cine MRI generally requires breath-holding, which can be problematic for many patients. Navigator echo techniques, particularly successful for free-breathing coronary MRA, are incompatible with the acquisition strategies and SSFP pulse sequences commonly used for cine MRI. The purpose of this work is to introduce a new self-gating technique deriving respiratory gating information directly from the raw imaging data acquired for segmented cine MRI. The respiratory self-gating technique uses interleaved radial k-space sampling to provide low-resolution images in real time during the free-breathing acquisition that are compared to target expiration images. Only the raw data-producing images with high correlation to the target images are included in the final high-resolution reconstruction. The self-gating technique produced cine series with no significant differences in quantitative image sharpness to series produced using comparable breath-held techniques. Because of the difficulties associated with breath-holding, the respiratory self-gating technique represents an important practical advance for cardiac MRI. , Inc.     

Vitamin A, E and C nutriture of elderly people in North Italy

The vitamin A, E and C nutritional status of 313 non institutionalized elderly people living in a small town and in an agricultural village of North Italy has been evaluated. From results obtained it is possible to say that all the population tested is at low risk for vitamin A deficiency, while 10-20% of people over 70 living in the small town have low levels of vitamin E. On the contrary, the nutritional status of ascorbic acid, where the levels are inadequate in more than 50% of the population, is worrying.     

The regional distribution of adenosine-regulating enzymes in the left and right ventricle walls of control and hypertrophic heart

Summary The transmural distribution of the adenosine-generating enzyme 5-nucleotidase (5N) and of the adenosine-degrading enzymes adenosine deaminase (ADA), AMP deaminase (AMP-D) and adenosine kinase (Ado-K) were determined across the walls of left and right ventricles of control and hypertrophic rat hearts.The enzyme distribution across the left ventricle wall (but not across the right wall) of normal hearts was not uniform: 5N activity shows its highest levels in the subepicardial and in the subendocardial regions, whereas all the other enzyme activities show their lowest levels. A similar pattern of transmural distribution was also detected in other mammalian species (ox and pig).In the experimental cardiac hypertrophy, caused by two different types of chronic cardiac overload, the levels and the profiles of transmural distribution of 5N and ADA enzyme activities may significantly change across the rat left ventricle wall.     

Characterization of mycobacterial isolates phylogenetically related to, but different from Mycobacterium simiae.

The use of high-performance liquid chromatography (HPLC) revealed four previously unreported profiles within a group of mycobacteria consisting of 14 clinical isolates. These mycobacteria, whose identification by conventional tests appeared problematic, mostly resembled Mycobacterium avium complex or Mycobacterium simiae. Genetic analysis revealed, within this group, six different nucleic acid sequences in a hypervariable 16S rRNA segment, but all the isolates appeared to be phylogenetically related to M. simiae. Six isolates representing the largest of groups defined by means of genetic sequencing turned out to belong to the newly described species Mycobacterium lentiflavum. Furthermore, three such clusters precisely coincided with three of those defined by HPLC, while the three remaining clusters shared almost identical HPLC profiles. All but one strain (which, although clearly not belonging to the M. avium complex, hybridized with specific commercial DNA probes) showed high-grade resistance to the majority of antimycobacterial drugs. Three of the isolates were clinically significant according to stringent criteria. Sophisticated techniques, like genetic sequencing or HPLC, by now seem indispensable for differentiating unusual and new mycobacteria from well-established ones.