Co-administration of polyanions with a phosphorothioate oligodeoxynucleotide (CGP 69846A): a role for the scavenger receptor in its in vivo disposition

The effects of co-administering polyanions on the pharmacokinetics of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A), and the role of scavenger receptors in its in vivo disposition, have been investigated. Following i.v. administration, CGP 69846A was rapidly cleared from the plasma and distributed amongst high (e.g. kidney, liver, spleen), low (e.g. skeletal muscle) and negligible (e.g. brain) accumulating tissues. In addition it was shown that: 1) dextran sulphate co-administration has a dose-dependent effect on the disposition of CGP 69846A; 2) CGP 69846A undergoes renal filtration and renal accumulation largely results from tubular reabsorption; 3) cross-inhibition studies are consistent with CGP 69846A being recognized by scavenger receptors in vitro and in vivo; and 4) the scavenger receptor may be an important determinant for the in vivo disposition of CGP 69846A in mice. These studies contribute toward an increased understanding of the mechanism underlying the pharmacokinetic behaviour of phosphorothioate oligodeoxynucleotides.     

Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate

OBJECTIVE: The objective of this study was to assess the degree of BP Tracking from childhood to adulthood and to evaluate whether high BP levels persist over time and progress to adult hypertension. PATIENTS AND METHODS: Two hundred and twenty-two healthy schoolchildren living in the North of Portugal were assessed at 17 year intervals, starting in 1979 (cohort 1) aged 5 to 18 years, and again in 1996 (cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x + y-z) /N/0.89, where x, y and z refer to the total number in the same, adjacent and remote trisections, respectively, and N = x + y + z. If Ti > 1 there is positive tracking. RESULTS AND CONCLUSIONS: For systolic and diastolic blood pressure, all Ti were greater than 1.0. All individuals that remained in the 3rd tertil, 17 years later, weigh more and are more obese than those of the 1st tertil. 56.6% of the individuals that belong to the 3rd tertil are now hypertensive, which means that a significant percentage of the children with high blood pressure in the first survey will be hypertensive in the future.     

Gas-liquid chromatography-mass spectrometry of hydroxy fatty acids as their methyl esters tert.-butyldimethylsilyl ethers

BACKGROUND: The objective of this paper is to illustrate the effect of a gap of 5 mm, an overlap of 5 mm and a perfect match on the dose distribution across the junction of tangential breast fields and adjacent supraclavicular and axillary fields. MATERIALS AND METHODS: For this purpose film dosimetry was applied to measure relative dose distributions in two sagittal planes in an anthropomorphic breast phantom having cork lungs, simulating a radiation therapy treatment of the breast and adjacent supraclavicular lymph nodes. Two different treatment techniques, an SSD match technique and a geometrically exact isocentric match technique, as routinely applied in the two institutes were examined. The three-dimensional treatment planning system of each institute was used to calculate the dose distribution in the match region of the supraclavicular fields and the two opposing tangential fields. The measured and calculated dose distributions were evaluated and compared along lines in two sagittal planes from the supraclavicular fields down to the tangential fields crossing the match planes. These dose distributions in the match region were extremely dependent on the set-up of the fields. RESULTS: Although the reproducibility of the film measurements was within 2%, it became clear that the set-up of the fields to achieve a gap of 5 mm, a perfect match or an overlap of 5 mm required a lot of attention, even when using a phantom. CONCLUSIONS: It can be concluded that in clinical practice, these set-up difficulties do influence the dose distribution in the match region much more than the systematic uncertainties in the dose calculation algorithms of the treatment planning systems and the type of treatment technique.     

Serious infections due to Pseudomonas aeruginosa

Infections due to Ps. aeruginosa are a problem in the tropics as in other parts of the world. Over a four year period, 15 patients attending University College Hospital, Ibadan, were proved to have septicaemia due to this organism and 13 patients died rapidly as a direct result of the infection. The two patients who survived the acute episode had received immediate treatment with at least one antibiotic active against Ps. aeruginosa: a third patient, who received immediate appropriate antibiotic therapy, was already suffering from aplastic anaemia and died rapidly despite treatment. The remaining patients received inappropriate antibiotic therapy because pseudomonas infection was not suspected at the time the diagnosis of septicaemia was made. Patients most at risk appear to be the very young and those with pre-existing malignant or other conditions affecting the defence mechanisms of the body: it is suggested that routine initial management of such patients should include a blood culture, followed by immediate treatment with an antibiotic combination that includes at least one agent likely to be active against Ps. aeruginosa. The development of medical services can lead to the introduction of ophthalmic or other operations on tissues that are highly susceptible to infection before facilities are provided for the maintenance of a pathogen-free environment. Following an outbreak of eye infection after cataract extractions, carried out in an old and unsatisfactory theatre, wide-spread room contamination was demonstrated with the same strains of Ps. aeruginosa that had been responsible for the clinical infections. Chemical disinfection of the theatre floor failed to eliminate the organisms, although other experiments suggested that the drying effect of air-conditioning would be successful in this respect. The wisdom of introducing such operations before the provision of adequate facilities is seriously questioned.     

Changes in the secretion of growth hormone in severely injured persons (author's transl)

The secretion of growth hormone was studied in 25 severely injured persons during the adaptive and convalescent stage. The ages of the patients varied between 9--65 years. During the first few days after the trauma hormone concentrations rose to up to 7--15 times their normal upper limits (about 10 mU/l). In some cases the hormone levels subsequently fell to the lower limits of normal. No attempt was made to calculate average values and the reasons for the omission are stated. The results are discussed with reference to the metabolic condition of the severely injured persons.