Library

Notes: A cylindrical arrangement of electrodes, together with control electronics, is described that provides uniform electric fields over cm3 volumes in a vacuum, whose angle and magnitude can be switched on a μs time scale. Full 360° field rotation is achieved, and the device allows access for particle or light beams from all sides. Both numerical and analytic descriptions of the general fields are given. Extension to full three-dimensional field control and other variations are described. The device, which was originally designed for crossed-beam collision experiments with keV energy ions and laser-excited Rydberg atoms in field-directed Stark states or coherent-elliptic states, may be more generally useful in atom trapping and cold collisions or in materials and surface science. © 1998 American Institute of Physics.

Notes: We report the case of a patient with a haeophilic pseudotumour of the ilium who developed chronic fistulation, 6 months after en-bloc resection. During the initial resection, the large defect in the iliac wing was filled with bone cement, which may have contributed to fistula formation. A second surgical procedure consisted of excision of the fistula and bone cement and the dead space was obliterated by bringing the gluteus medius muscle into the defect. The fistula recurred, however. Re-excision of the fistula and obliteration of the dead space by a pedicled rectus abdominis muscle flap resulted in eradication of the fistula. We emphasize the importance of obliteration of dead space, resulting from large pseudotumour resection. The use of bone cement is not advocated. If a fistula does occur, a pedicled rectus abdominis muscle flap may be considered.

Notes: We evaluated the long-term results of three total hip and nine total knee arthroplasties in nine haemophilic patients with disabling pain and end-stage arthropathy. These patients have been followed over a period of 2–12 years (mean 6.9). One patient had a post-operative haematoma, which was evacuated; two patients required manipulation of the knee because of a limited range of motion. There were no infections. At follow-up, all but two patients were completely free of pain; two patients had occasional pain. The functional improvement was impressive with an average increase in the knee score from 37 to 80 points post-operatively. The hip score increased from 36 to 85 points. The range of motion was increased in seven joints, unchanged in two joints and decreased in three. One total hip arthroplasty was revised after 9 years for aseptic loosening. One total knee demonstrated nonprogressive radiographic evidence of aseptic loosening. Median consumption of coagulation factor concentrate in severe haemophiliacs decreased from 47.00 U yr−1 (range 16.000–144.000) before surgery, to 25.000 U yr−1 (range 18.000–132.000) at 2 years after surgery. Conclusion: hip and knee arthroplasty is a valuable option in symptomatic haemophilic patients with disabling arthropathy, in order to obtain pain relief and functional improvement. It is associated with a low rate of complications and may reduce the need for substitution of factor VIII and IX.

Notes: The meta operon of the Pseudomonas putida TOL plasmid (pWW0) encodes all enzymes of a meta-cleavage pathway for the metabolism of benzoic acids to Krebs-cycle intermediates. We have determined and analysed the nucleic acid sequence of a 3442 bp region of the meta operon containing the xylGFJ genes whose products are involved in the post meta-ring fission transformation of catechols. Homology analysis of the xylGFJ gene products revealed evidence of biochemical relatedness, suggested enzymatic mechanisms, and permitted us to propose evolutionary events which may have generated the current variety of aromatic degradative pathways.The xylG gene, which specifies 2-hydroxymuconic semialdehyde dehydrogenase (HMSD), was found to encode a protein of 51.7 kDa. The predicted protein sequence exhibits significant homology to eukaryotic aldehyde dehydrogenases (ADHs) and to the products of two other Pseudomonas catabolic genes, i.e. xylC and alkH. Expansion of the ADH superfamily to include these prokaryotic enzymes permitted a broader analysis of functionally critical ADH residues and phylogenetic relationships among superfamily members. The importance of three regions of these enzymes previously thought to be critical to ADH activity was reinforced by this analysis. However glutamine-487, also thought to be critical, is less well conserved. The revised ADH phylogeny proposed here suggests early catabolic ADH divergence with subsequent interkingdom gene exchange.The xylF gene, which specifies 2-hydroxymuconic semialdehyde hydrolase (HMSH), was delineated by N-terminal sequence analysis of the purified gene product and is shown to encode a protein of 30.6 kDa. Homology analysis revealed sequence similarity to a chromosomally encoded serine hydrolase, especially in the region of the previously identified active-site serine residue, suggesting that HMSH may also possess a serine hydrolytic enzymatic mechanism.Likewise, the xylJ gene, which specifies 2-hydroxypent-2,4-dienoate hydratase (HPH), was delineated by N-terminal sequence analysis of purified HPH, and was found to encode a 23.9 kDa protein.Sequence comparisons revealed that both HMSH and HPH have analogues in the tod gene cluster, which specifies a toluene/benzene degradative pathway. Although the newly identified todF and todJ genes had been at least partially sequenced (Zylstra and Gibson, 1989), the open reading frames had not been positively identified. The presence of todJ provides strong evidence that the reactions following ring fission in the tod pathway are identical to those of the TOL pathway.The meta operon is one of the longest prokaryotic operons known. The structure of the xylGFJ genes displays short intergenic regions and overlapping translational signals. This genetic organization suggests a mechanism of post-transcriptional regulation whereby translational competency of downstream genes might be enhanced and lengthy transcripts stabilized against ribonucleolytic attack. Such an operon structure may have evolved to facilitate adequate expression of promoter distal genes of long operons.

Notes: "Diskussion"

Notes: Proton-pump inhibitors are acid-labile, and require an enteric coating to protect them from degradation in the stomach when given orally. However, this leads to delayed absorption and onset of action of the proton-pump inhibitor.This article aims to review the similarities and differences between the various formulations of delayed release proton-pump inhibitors. Delayed-release omeprazole and delayed-release lansoprazole have been suspended in sodium bicarbonate for tube administration; however, for omeprazole, absorption is further impaired and antisecretory effects are disappointing. Although such formulations may be more convenient for clinical use in certain patient groups, absorption of the proton-pump inhibitor is still influenced by residual enteric coating. There are few differences among the currently available delayed-release proton-pump inhibitors with respect to their pharmacodynamic effects during chronic administration. There are minor formulation-based pharmacokinetic differences among these agents, primarily reflected in their bioavailability following the first few doses.Differences in bioavailability may explain slight differences in the rate of onset of maximal antisecretory effect. However, minor pharmacodynamic and pharmacokinetic differences are not associated with meaningful differences in clinical outcomes.

Notes: Proton pump inhibitors are now considered the mainstay of treatment for acid-related disease. Although all proton pump inhibitors are highly effective, the antisecretory effects of different drugs in this class are not completely consistent across patients. One reason for this is the acid-suppressing effect of Helicobacter pylori infection, which may augment the actions of proton pump inhibitors. A second important reason for interpatient variability of the effects of proton pump inhibitors on acid secretion involves genetically determined differences in the metabolism of these drugs. This article focuses on the impact of genetic polymorphism of cytochrome P450 (CYP)2C19 on the pharmacokinetics and pharmacodynamics of proton pump inhibitors, particularly rabeprazole. Results reviewed indicate that the metabolism and pharmacokinetics of rabeprazole differ significantly from those of other proton pump inhibitors. Most importantly, the clearance of rabeprazole is largely nonenzymatic and less dependent on CYP2C19 than other drugs in its class. This results in greater consistency of pharmacokinetics for rabeprazole across a wide range of patients with acid-related disease, particularly those with different CYP2C19 genotypes. The pharmacodynamic profile for rabeprazole is also characterized by more rapid suppression of gastric acid secretion than with other proton pump inhibitors, which is also independent of CYP2C19 genotype. The favourable pharmacokinetic/pharmacodynamic profile for rabeprazole has been shown to result in high eradication rates for H. pylori in both normal and poor metabolizers. Pharmacodynamic results have also suggested that rabeprazole may be better suited than omeprazole as on-demand therapy for symptomatic gastro-oesophageal reflux disease. Finally, the use of rabeprazole is not complicated by clinically significant drug–drug interactions of the type that have been reported for omeprazole.