[Preoperative Information: What Do Patients Want to Know?]. / Die präoperative Aufklärung: Was wünschen sich Patienten?

BACKGROUND: Aimed at supporting patient information, media forms were developed. While doing so patient views were predominantly not considered. Moreover, for one of the most common surgical procedures, herniated disk surgery, there rarely exists appropriate information material. PATIENTS AND METHODS: 29 people with experience of back pain were recruited to participate in focus group interviews, where conditions of satisfying consultations and needs regarding the design of an education film for herniated disk surgery were analysed. RESULTS: Frame conditions, desired education media and factors relating to the physician compose three complexes of general satisfaction criteria. Needs in terms of form and content design of an education film were discussed and registered in detail. CONCLUSION: Existing guidelines considering patient education are extensively consistent with patients' desires and should be implemented obligatorily. The use of audio-visual media as well as medical students' and physicians' training in soft skills requires expansion.

Investigations into the decomposition of aminoacyl-substituted monosaccharide scaffolds from a drug discovery library.

This study investigated the unexpected decomposition and associated intermediates of compound 1, a specific member of a drug discovery library based on a monosaccharide scaffold. LC/MS and NMR spectroscopic analyses indicated that, under acidic conditions, 1 can be converted into the 4-aminogalactoside 2, due to cleavage of the 4-aminobutanoyl side chain. The reaction occurs most likely through an initial intramolecular amino­amide interaction, followed by an N- to O-acyl transfer of the side chain from C-4 to the C-6 position to form an ester intermediate (5), detectable by NMR, and subsequent hydrolysis. Similar decomposition reactions could be induced in selected compounds with similar structures, containing a free hydroxyl group at C-6 and a 4-aminobutanoyl side chain at C-4 of an aminogalactoside. Furthermore, three model compounds were synthesized without a C-6 hydroxyl group and with different length aminoalkanoyl side chains at the C-4 position. The model compounds all decomposed under acidic conditions, but at different rates and much slower when compared with compound 1, suggesting that both the C-6 hydroxyl group and the length of the side chain have an influence on stability.

Effects of inulin and lactulose on the intestinal morphology of calves.

For some time now prebiotics have been proposed to improve health by stimulation of beneficial bacteria in the intestine of humans and animals. The current study is aiming to show effects of feeding of either 2% inulin or 2% lactulose in milk replacer on performance and intestinal morphology of male Holstein-Friesian calves. After 20 weeks of feeding inulin led to significantly higher daily weight gains than lactulose while control animals ranged between the experimental feedings. Ingestion of milk replacer was reduced in lactulose treated animals. Additionally differences of villus height in jejunum (P = 0.07) and ileum (P = 0.03) could be found with an increase for lactulose treated animals and a decrease for inulin treated animals. In ileum the density of proliferative epithelial cells tended to be lower in inulin treated and higher in lactulose treated animals (P = 0.08). Both inulin and lactulose tended to decrease the quantity of goblet cells in the tips of ileal villi (P = 0.07). Both prebiotics can affect performance and intestinal morphology of calves and may as such affect animal health. But effects differ between substances.

The PG500 series: novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy.

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Correlation between pulse wave velocity and other measures of arterial stiffness in chronic kidney disease.

AIM: Pulse wave velocity (PWV), augmentation index (AIx) and time to first wave reflection (Tr) are all measures of arterial stiffness, but whether these parameters behave similarly in different populations is not well-understood. Given the large burden of cardiovascular disease in individuals with chronic kidney disease (CKD), assessing the relationship between vascular stiffness parameters in this population is important. METHOD: A subset of 152 participants enrolled in the Chronic Renal Insufficiency Cohort Study had vascular stiffness parameters (aortic PWV, central AIx, and Tr) measured using the SphygmoCor system. Linear association between these parameters was assessed using Pearson correlation coefficients. Reproducibility across operators of the device was also tested within individuals. RESULTS: Association was largest between PWV and heart rate-adjusted AIx (AIx-75). The correlation coefficient was 0.371 (p = 0.0003) for ideal studies and 0.305 (p = 0.0001) for all technically acceptable studies. The association between ideal PWV and AIx-75 measurements was 0.361 (p = 0.005) for men and 0.423 (p = 0.01) for women. Bland-Altman plots comparing the mean value of PWV (n = 31) or AIx-75 (n = 21) when measured by 2 different individuals against the difference in their respective values demonstrate that both measures of arterial stiffness are reproducible across multiple technicians. CONCLUSIONS: Thus, we conclude that PWV and AIx-75, despite measuring different quantities in different units, are related measures of arterial stiffness and are reproducible across multiple operators in the population with CKD.

Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity.

We have performed a long-term study into the use of a lipophilic amino-acid dendrimer to deliver an anti-vascular endothelial growth factor (VEGF) oligonucleotide (ODN-1) into the eyes of rats and inhibit laser-induced choroidal neovascularization (CNV). In addition, the uptake, distribution and retinal tolerance of the dendrimer plus oligonucleotide conjugates were examined. Analysis of fluorescein angiograms of laser photocoagulated eyes revealed that dendrimer plus ODN-1 significantly inhibited (P<0.05) the development of CNV for 4-6 months by up to 95% in the initial stages. Eyes similarly injected with ODN-1 alone showed no significant difference (P>0.05) in mean severity score at 2 months (2.86+/-0.09), 4 months (2.15+/-0.17) or 6 months (2.7+/-0.12) compared to the vehicle-injected controls. Furthermore, we showed that intravitreally injected ODN-1 tagged with 6-fam was absorbed by a wide area of the retina and penetrated all of the retinal cell layers to the retinal pigment epithelium. Ophthalmological examinations indicated that the dendrimers plus ODN-1 conjugates were well tolerated in vivo, which was later confirmed using immunohistochemistry, which showed no observable increase in antigens associated with inflammation. We conclude that the use of such dendrimers may provide a viable mechanism for the delivery of therapeutic oligonucleotides for the treatment of angiogenic eye diseases.

Synthesis of neoglycoproteins containing D-glycero-D-talo-oct-2-ulopyranosylonic acid (Ko) ligands corresponding to core units from Burkholderia and Acinetobacter lipopolysaccharide.

Glycal esters of Kdo derivatives were converted into 2,3-anhydro intermediates, which were transformed into D-glycero-D-talo-oct-2-ulopyranosylonic acid (Ko), as well as 3-O- and 4-O-p-nitrobenzoyl-Ko derivatives. The exo-allyl orthoester derivative, methyl [5,7,8-tri-O-acetyl-4-O-(4-nitrobenzoyl)-2,3-O-[(1-exo-allyloxy)-ethylidene]-D-glycero-beta-D-talo-oct-2-ulopyranos]onate, prepared from the 4-O-pNBz-protected Ko derivative, was elaborated into the alpha-Ko allyl ketoside, the reducing disaccharide alpha-Kdop-(2-->4)-Ko and the disaccharide alpha-Kdop-(2-->4)-Kop-(2-->OAll). Conversely, methyl[4,5,7,8-tetra-O-acetyl-3-O-(4-nitrobenzoyl)-alpha-D-glycero-D-talo-2-octulopyranosyl bromide]onate [Carbohydr. Res., 244 (1993) 69-84], was coupled with a Kdo acceptor to give the disaccharide alpha-Kop-(2-->4)-Kdop-(2-->OAll) after orthoester rearrangement and deprotection. The allyl glycosides were treated with cysteamine and converted into neoglycoproteins. The ligands correspond to inner core units from Acinetobacter haemolyticus and Burkholderia cepacia lipopolysaccharides.