Hypersensitivity to platinum salts according to BRCA status in ovarian cancer: A retrospective analysis of clinical outcomes and systematic review of literature.

BACKGROUND: Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status. PATIENTS AND METHODS: We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series. RESULTS: Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. [9% vs 18%, p = 0.019] and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00-3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004-0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant. CONCLUSIONS: In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.

Kinetic modeling of the SWNT growth by CO disproportionation on CoMo catalysts.

A kinetic model has been developed to describe the growth of single-walled carbon nanotubes (SWNT) in the CoMoCAT method, which is based on the disproportionation of CO on supported CoMo catalysts. The model attempts to capture mathematically the different stages involved in this method: (i) catalyst activation or in-situ creation of active sites, i.e., reduced Co clusters by transformation of CoMoOx precursor species, or oxidized sites; (ii) CO decomposition over active sites, which increases the surface fugacity of carbon until reaching a certain threshold; (iii) nucleation of ordered forms of carbon; (iv) C diffusion (both across the surface and into the metal particle); (v) SWNT growth; (vi) termination, by either deactivation of the catalyst active sites or by increase in the carbon concentration at the metal/SWNT interface, approaching that of the metal/gas interface and eliminating the driving force for diffusion. Previous investigations have only explained the growth termination by the former. Here, we emphasize the possible contribution of the later and propose a novel "hindrance factor" to quantify the effect of nanotube interaction with its surroundings on the growth termination. To test the kinetic model and obtain typical values of the physical parameters, experiments have been conducted on a CoMo/SiO2 catalyst in a laboratory flow reactor, in which the rate of carbon deposition was continuously evaluated by the direct measurement of the CO2 evolution as a function of time. The experimental data are fitted very well with model.

Quantitative analysis of glycosaminoglycans in urothelium and bladder wall of calf.

Glycosaminoglycans (GAG) were described by histochemical staining procedures in the normal urothelium of the urinary bladder; they are supposed to be involved in the antibacterial defense mechanism. Our quantitative analysis, however, demonstrated only heparan sulfate in the normal calf urothelium (less than 600 nmol/Gm d.wt.); only trace amounts of other GAG were to be analyzed. High concentrations of GAG were found in the submucosa and muscle layers as to be expected in mesoderm originating tissues. According to these results there were no GAG with the exception of heparan sulfate at the surface of the normal urothelium; therefore, glycoproteins detected in mumol/Gm d.wt. ranges are more likely to be involved in the antibacterial defense mechanism.

Studies on the polydispersity and heterogeneity of proteokeratan sulfate from calf and porcine cornea.

After proteolysis of the calf and porcine corneae with papain 66 (calf) and 56 (hog) polysaccharide-containing fractions were obtained by chromatography on Dowex 1X2 and fractionating precipitation with ethanol (calf) and by chromatography on Dowex 1X2 and CPC-cellulose (hog). The sulfatation degrees (mol sulfate/mol hexosamine) and molecular weights (Mw) of 13 peptidokeratan sulfate fractions from calf cornea and of 9 such fractions from porcine cornea were 0.41-1.25 (Mw 3200-21 500), and 0.42-1.41 (Mw = 4900-25 600), respectively. It was found that the sulfatation degree increases more than proportionally with the chain-length. More than 90% of total keratan sulfate in both cases contain 2-3 mannose and 5-9 amino acid molecules per peptidokeratan sulfate molecule. About 30% of the corepeptide amino acids were asparagine or aspartic acid. More than 90% of the peptidokeratan sulfates from porcine cornea exhibits chain lengths of 31-47 disaccharide units. Two oligosaccharide peptides were isolated from porcine cornea, both being sulfate-free. Besides a core peptide of about 9 amino acids (2 Asx) one of them showed a sugar composition very similar to that of the binding-region from corneal keratan sulfate accord. to Keller, R., Stein, T., Stuhlsatz, H.W., Greiling, H., Ohst, E., Müller, E., & Scharf, H.-D. (1981) Hoppe-Seyler's Z. Physiol. Chem. 362, 327-336: 3 Man, 2 Gal, 4 GlcNAc. The calculated molecular weight based on 3 mannose residues (Mw = 2 600) agrees with that determined by gel chromatography. The second oligosaccharide peptide was homogeneous on electrophoresis and contained the constituents of the linkage region from chondroitin sulfate beside those from keratan sulfate. Based on 4 mannose residues the calculated molecular weight (4 300) is in agreement with that from gel chromatography. The sequence Asn-X-Asx starting with the binding-Asn is postulated in the core protein of proteokeratan sulfate from amino acid analyses of the corneal peptidokeratan sulfate fractions.

[Total and partial parenteral feeding of premature and newborn infants: nitrogen balances and serum amino acid chromatograms]. / Totale und partielle parenterale Ernährung bei früh- und Neugeborenen: Stickstoffbilanzen und Serumaminosäurenchromatogramme.

We report upon 30 critically ill premature and newborn infants (mean birth weight: 2,350 g). In all cases we applied initially total parenteral nutrition with increasing supplies, subsequently partial parenteral nutrition. Donors of nutritive substance and calories were a 6% mother-milk adapted amino-acid solution, a glucose solution 10% and 20% and a 20% lipid emulsion. Serum electrolytes, urea, glucose, serum aminograms and nitrogen balances were determined at regular intervals. Serum aminograms were found altogether acceptable in relation to those of breast-fed newborns and small infants and to normal values, which we evaluated among 45 premature and newborn infants before supplying protein.