[Opioid rotation: from theory to practice. Interdisciplinary recommendations from the Geneva University Hospitals pain network]. / Rotation des opioïdes: de ta théorie à la pratique. Recommandations interdisciptinaires du réseau douleur des HUG.

Opioids are widely used to treat moderate to severe pain of cancer or non cancer origin. Although opioids provide an adequate analgesia in many patients, their use can be limited by inefficacy and/or intolerable side effects. Opioid rotation is one of the strategies that have been proposed to overcome these therapeutic difficulties. This article revisits the concept of opioid rotation, from pharmacological rational to clinical application.

Cryopreservation of ovarian tissue: an emerging technology for female germline preservation of endangered species and breeds.

Many hundreds of exotic species and domestic animal breeds have been lost over the course of the last few decades. In order to avoid a similar fate to other animals threatened with extinction, it is crucial to develop and apply rescue strategies to ensure their survival for the future. One option as a safeguard measure is the cryopreservation of the main source of female gametes enclosed within the ovary: the primordial follicles. So far, there are three options to cryopreserve small ovarian follicles: whole ovary, ovarian cortical tissue or isolated follicles, with the use of slow freezing or vitrification methods. After cryopreservation, the harvested material can be transplanted or cultured, with the aim to produce mature fertilizable oocytes. The objective of this review is to summarize the current status of the cryopreservation of ovarian tissue in domestic species and non-endangered wild mammals as model for threatened and endangered species and breeds, and to provide new insights into techniques that can be applied in the future.

Poor late prognosis of bleeding peptic ulcer.

BACKGROUND AND AIMS: Long-term course of peptic ulcer bleeding is unclear. Because of a more aged and more diseased ulcer population, the long-term prognosis may be expected as poor. MATERIALS AND METHODS: In a prospective study, all patients with peptic ulcer bleeding treated at the Department of Surgery of the Heinrich-Heine-University in Düsseldorf were included between 1986 and 1995. Follow-up covered hospital mortality, 1-month mortality, 1-year mortality, and 5-years mortality. Significant prognostic parameters for death were investigated in univariate and multivariate analysis. RESULTS: One hundred and seventy-one out of 192 patients with peptic ulcer bleeding could be followed up. One-month mortality was similar to hospital mortality with 12.3%, 1-year mortality was 28.7%, and the 5-years mortality was 46.8%! In univariate analysis, statistically significant prognostic factors for death were ages beyond 70 years, concomitant diseases, risk-related drugs, postinterventional complications, and recurrent bleeding. In multivariate analysis, age, postinterventional complications, and type of admission were statistically significant parameters for death. CONCLUSION: Long-term prognosis of peptic ulcer bleeding is poor! The majority of deaths after hospital stay is probably not because of ulcer bleeding, but because of more aged patients with severe concomitant diseases.

Prevention of recurrent bacterial urinary tract infections by intravesical instillation of hyaluronic acid.

OBJECTIVE: To evaluate the efficacy of vesical instillation of hyaluronic acid against recurrent urinary tract infections. METHODS: Twenty women with a history of recurrent urinary tract infections each received 9 intravesical instillations of hyaluronic acid over 6 months. Their status was assessed prospectively over 47.6 weeks and compared with a retrospective review of patient charts covering 36.2+/-6.2 weeks. RESULTS: The total numbers of urinary tract infections were 67 before and 10 after treatment (p<0.001). Thirteen patients (65%) were free of recurrences until the end of the study. One had a recurrence during treatment, and 6 (30%) during follow-up. The number of infections per year per patient was reduced from 4.99+/-0.92 to 0.56+/-0.82 (p<0.001). In women with recurrences, time to recurrence was 178.3+/-25.5 days, compared with 76.7+/-24.6 days before treatment (p<0.001). CONCLUSION: Intravesical instillation of hyaluronic acid is effective in preventing recurrent urinary tract infections.

Low abundance of Escherichia coli microsatellites is associated with an extremely low mutation rate.

It is widely assumed that microsatellites are generated by replication slippage, a mutation process specific to repetitive DNA. Consistent with their high mutation rate, microsatellites are highly abundant in most eukaryotic genomes. In Escherichia coli, however, microsatellites are rare and short despite the fact that a high microsatellite mutation rate was described. We show that this high microsatellite instability depends on the presence of the F-plasmid. E. coli cells lacking the F-plasmid have extremely low microsatellite mutation rates. This result provides a possible explanation for the genome-wide low density of microsatellites in E. coli. Furthermore, we show that the F-plasmid induced microsatellite instability is independent of the mismatch repair pathway.

[Cementless stems of the hip. Current status]. / Zementfreie Hüftschäfte. Aktueller Stand.

Optimal fixation of cementless stems is a precondition for long-lasting stability. Thus, anchorage, stabilizers, material and surface are of essential importance. To achieve primary stability, good rotational, tilting and axial stability is necessary. Stabilizers such as fins and ribs optimize stability. The CCD-angle and length of neck-axis determine the offset (laterality), leg-length and center of rotation. The stem, is responsible for the fixation of the prosthesis and for transmitting forces to the bone. The types of fixation are epiphyseal (the femoral head is covered by a cup prosthesis), metaphyseal and meta-diaphyseal (with straight or anatomically shaped monoblock-prostheses of different lengths, modular and custom-made prostheses) and diaphyseal (using predominantly modular systems). Titanium alloys are the predominate material for cementless stems. The surfaces are generally corundum-blasted or plasma sprayed. For metaphyseal and meta-diaphyseal stems, survival rates from 95 to 98% have been reached after 15 years. Diaphyseal-fixed stems have mid-term survival-rates of 92-99%.

Propolis solution for the treatment of chronic vaginitis.

OBJECTIVE: To evaluate the efficacy of 5% propolis solution in recurrent vaginitis. METHOD: Fifty-four patients with recurrent vaginal infections having undergone at least one cycle of antibiotic treatment were instructed to apply a 5% aqueous propolis solution as a vaginal douche for seven days. Vaginal smears and specific symptoms were evaluated at baseline and 14 days after treatment. Long-term well-being was assessed by telephone interview six months after follow-up. RESULT: At the follow-up, the vaginal smears of 41 patients (75.9%) had improved. Forty-seven patients (87%) reported reliefs concerning at least one complaint. Associated improvement of smear and well-being was observed in 36 women (66.7%). After 6 months, 33 patients (61.1%) were satisfied with their condition without having undergone further treatment. CONCLUSION: Propolis may have a role as an alternative treatment for chronic vaginal infection.

Anatomically adapted, HA coated SBG stem--ten years of successful implantation.

For stable implantation of anatomically conforming femur prostheses, modifications that accommodate curving and torsion are necessary. In accordance to this concept, the anatomically shaped SBG stem has been developed. The first consecutive implantations were evaluated. 194 primary arthroplasties with uncemented anatomical, HA coated SBG stems were performed. Mean patient age was 61 years. 143 patients with 151 (78%) SBG stems were followed-up clinically and radiologically after an average of 10 (9-11) years. So far, only one implant had to be revised. Survivorship with revision of the femoral component is 99.5% at ten years. The mean postoperative Harris Hip Score was 92. Patients over 75 years had a score of 89; younger patients under 40 years scored 94. Sclerotic lines were seen in zone I or VII in 8%. Minor femoral remodeling (Type 1) occurred proximally in 75%. Minor thickening of the femur at the level of the tip of the prosthesis could be observed in 27% of the cases. There is no correlation between compacta thickening and clinical symptoms (p=0.15). The anatomical shape, the oval diameter and the longitudinal grooves secure stable primary fixation. Together with the HA coating, which enhances osseointegration, the SBG stem has a high success rate in the medium and long term.

[Cement-free hip cups. Current status]. / Zementfreie Hüftpfannen. Aktueller Stand.

Important criteria for stable cup fixation are the type of anchor system and stabilizers,cup form and the material and surface structure. Different fixation systems are manifest in pressfit and threaded cups. Pressfit implants are oversized and lead to equatorial jamming. For additional fixation, and to improve stability, screws, pegs, rings, fins, spikes or hollow cylinders are used. In threaded cups, thread geometry is decisive for the cup's performance during the screw-in process and positioning. The hemispheric shape of the cups requires less bone resection and the position of the implant can be arbitrarily selected. The conical shape guarantees high tilting stability. Most implants are made of pure titanium or a titanium-aluminum alloy. A rough surface area - produced by corundum blasting, titanium-plasma spray, titanium balls, nets or other grid designs - is essential for osseointegration. The results of second generation pressfit and threaded cups with 10 year survival rates of 93-100% are persuasive.

Factors influencing the revision rate of Zweymueller acetabular cup.

Between January 1986 and December 1988, we implanted 220 conical-shaped Zweymueller threaded cups in 202 patients whose average age was 65 (33-83) years. The average thickness of the polyethylene (PE) insert was 8.0 (5.4-11.9) mm. In 142 cases, the corresponding femoral head was a 32 mm Al2O3 head. We followed 157 patients for a mean of 9.2 (1-16) years. Nine cups were revised and ten PE inserts replaced after an average of 11.9 (10-13.3) years. With cup revision alone considered as failure, the survival rate after 13 years was 89%. When both cup and insert revisions were considered failures, the survival rate decreased to 72% after 13 years. Patients younger than 60 years had a significantly higher rate of insert revision. Cup size 55 showed significantly more revisions in comparison to larger sizes. Using Cox regression model, neither gender, body mass index, nor material were risks factors leading to cup revision.

[Acetabular shape and cementless cups. Comparison of osteoarthritic hips and implant design]. / Acetabulumform und zementfreie Hüftpfannen. Vergleich von Arthroseacetabula mit Implantatformen.

The anatomy of the hip must be taken into account in order to ensure primary stability of cementless acetabular implants. In this study we analyzed the shapes of osteoarthritic acetabula and compared these to normal non-degenerative acetabula and to pressfit implants. We measured 92 acetabula with osteoarthritic deformations and 35 non-degenerative acetabula. Bone tissue samples from 50 osteoarthritic acetabula were microradiographically analyzed. Furthermore, the size of the entrance plane of 37 pressfit cups was determined. The craniocaudal and ventrodorsal diameters of osteoarthritic acetabula correlate strongly ( r=0.87). In craniocaudal direction, the acetabular diameter correlates significantly to both the radius of the lunate surface ( r=0.42) and the acetabular base ( r=0.54). Osteoarthritic acetabula have a deeper shape as degeneration increases and the entrance plane becomes significantly more circular ( p<0.05). When comparing osteoarthritic and non-arthrotic acetabula, the following values differ significantly (p<0.05): craniocaudal radius of the acetabular base, craniocaudal and ventrodorsal radius of the lunate surface, and ventrodorsal divergence between lunate surface and acetabular base. To reconstruct an acetabular offset which concurs with central points of the femoral head and the radius of the lunate surface, the level of the insert's entrance plane must be outside the entrance planes of the cup and acetabulum. The rims of hemispheric cups need to be trimmed to prevent these cups from extending beyond the acetabular rim.

Cryopreservation of a whole ovary as a strategy for restoring ovarian function.

PURPOSE: To evaluate whether a total ovary can successfully be cryopreserved and thawed under maintenance of high proportions of structurally normal primordial follicles. METHODS: Porcine ovaries were explanted immediately after slaughtery. Ten ovaries were cooled to -196 degrees C using cryoprotective solution and a computer-controlled freezing technique. Five contralateral ovaries were fixed with formalin for histological examination, the five remaining ovaries were directly plunged in liquid nitrogen. After three weeks of storage, frozen ovaries were thawed and examined by light and electron microscopy. Viability was assessed by evaluation of intact primordial follicles with respect to cellular and intracellular structures. RESULTS: Histological viability of primordial follicles in computer-frozen ovaries was 84.4% (76.1-90.6%), as compared to non-frozen control samples (92-100%; mean 97.6%) and to ovaries plunged in liquid nitrogen without cryoprotection 21.1% (4.5-35.0%). CONCLUSIONS: Cryopreservation of whole ovaries may present a feasible way to maintain high numbers of viable primordial follicles in ovarian tissue retransplantation.

Criteria for success with threaded cups (design, material and modularity).

PURPOSE OF THE STUDY: Over a period of three generations, threaded cups were developed and have become viable contemporary cementless hip implants. A few implants already have a high success rate over the mid and long term. Aim of this study was to evaluate contemporary threaded cups. MATERIAL AND METHODS: 30 of the second and third generation cups were systematically analyzed and measured using by a no-touch light section technique. Construction of inner form was determined with half sections. RESULTS: Approximately 50% have a conical shape, although there is a trend towards a more anatomical shape. 83% of the cups have a height up to 23% smaller than the radius. Only conical threaded cups have a relatively thin and constant wall thickness (1 mm-1.8 mm). Corundum blasted pure titanium, titanium alloys or HA coated implants are considered the standard materials. The insert is pre-assembled in two implants, otherwise the cups have modular inserts. Total ceramic inserts are found in four cups. Ceramic inserts with a sandwich construction are found in six cups. One cup has a full-metal insert. All other cups with metal-metal inserts have a sandwich construction. DISCUSSION: The studies by Kody (6) and our own studies (10) show that the V-cut threads have high values for turning moment and tilting stability. CONCLUSION: The screw-in behavior of threaded cups is largely determined by the design of the threads. Material and surface of threaded cups influence osseointegration and therefore long-term results. Contemporary threaded cups have a narrow V-cut and saw threads or flat threads with depths up to 3 mm, on average 4 turns, and pith values of approximately 4.5 mm. Three generations of threaded cups development were necessary to procure the current form with highly satisfactory mid- and long-term results.

[Design, construction and modularity of pressure-fit acetabular cups]. / Form, Konstruktion und Modularität von Pressfit-Hüftpfannen.

To enable a comparison of different pressfit acetabular cups objective criteria are essential. The aim of this study is to describe the design features of this type of cup and to analyse currently available cups. 30 implants were systematically measured and analysed. The mean surface roughness (Ra) was determined and configurations established with the light section technique. For further evaluation the cups were transversely sectioned. The cups are made of pure titanium, titanium alloy or polyethylene coated with titanium. Five implants take the form of monoblocks. The configuration is predominately (n = 25) flattened spherical. The size of eight cups corresponds to the outer diameter, 19 cups have a larger outer diameter (overdimensioning), 3 cups have a smaller outer diameter (underdimensioning). The magnitude of overdimensioning is, on average, 1.9%. 9 cups are provided with plugs, hollow cylinders, fins or rings as outer stabilizers. Surface roughness achieved with corundum blasting is 6.8 microns. Titanium porous-coated implants have a surface roughness of 21-32 microns. 24 cups have polyethylene inserts, most of which are snap-fixed with equatorial lips. For 16 cups, full-ceramic inserts are available. 4 cups have a metal insert. Titanium implants with structured or HAC-coated surfaces have become the accepted standard for cementless acetabular cup implantation. Together with ceramic, metal, or modified polyethylene inserts they meet the requirement for permanent osteo-integrative stability.

[Modification of form, material and modularity of threaded acetabulum cups]. / Modifikationen von Form, Material und Modularität der Schraubpfannen.

The fixation principle of threaded cups ensures high primary stability. Inadequate results with first-generation threaded cups led to modifications of surface machining. 10 threaded cups of the first generation, and 27 of the second and third generations were systematically analysed and their shapes measured using a no-touch light section technique. In addition, measurements of surface roughness were performed. Implants of the first generation made of polyethylene, ceramic or cobalt-chrome have an average surface roughness (Ra) of 1.5 microns. Approximately one-half of these implants have a conical shape, and one-third a height that is greater than the radius. Threaded cups of the second generation are made either of CP-titanium or titanium alloy. The average corundum-blasted surface roughness is 4.5 microns. Hydroxyapatite-coated (HA) implants have a surface roughness of 5.0 microns. Approximately 45% of the implants have a conical, biconical or flattened-conical shape, while one-third are of hemispherical shape. Approximately 90% of the cups have a height that is up to 23% smaller than the radius. A few cups have a height that approximates the radius. Implants of the third generation with identical surface structure can be supplied with crosslinked-polyethylene inlays or, optionally, with metal/metal or ceramic/ceramic contact surfaces. Primary stability, biocompatible materials and a structured surface are essential for ensuring osseointegration over the long-term. Corundum-blasted pure titanium or titanium alloys with corundum-blasted or HA-coated implants can be considered standard for these cups.

Teaching laparoscopic cholecystectomy: do beginners adversely affect the outcome of the operation?

OBJECTIVE: To evaluate the safety of elective laparoscopic cholecystectomy (LC) as a supervised teaching procedure. DESIGN: Prospectively documented series, retrospective analysis. SETTING: University teaching hospital, Austria. SUBJECTS: 581 consecutive patients who underwent elective LC for symptomatic cholelithiasis between January 1993 and December 1997. INTERVENTIONS: LC were allocated to three groups: the first (n = 91) were done by supervised beginners (who had done fewer than 11 LC), the second (n = 249) by supervised trainees who had a little experience (they had done more than 10 but fewer than 51 LC), and the third group (n = 241) who were experienced surgeons (they had done more than 50 LC). MAIN OUTCOME MEASURES: Minor and major complications, conversion and reoperation rate, length of operation and postoperative hospital stay. RESULTS: The minor intraoperative complication rates were 36/91 (40%), 115/249 (46%) and 49/241 (20%), respectively (p < 0.001 when experienced surgeons were compared with the 2 trainees' groups). There were no significant differences between the three groups regarding major complications (1/91, 4/249 and 4/241), conversions (5/91, 21/249, and 17/241) and reoperation rate (1/91, 3/249 and 3/241), median (range) length of operation 82 (24-159), 84 (25-249) and 82 (21-234) minutes and hospital stay 4 (3-19), 4 (3-11) and 4 (2-15) days. CONCLUSION: Elective LC for symptomatic cholelithiasis done by trainees under supervision does not increase surgical morbidity.

Efficacy and safety of thoracoscopic sympathicotomy for hyperhidrosis of the upper limb. Results of 734 sympathicotomies.

BACKGROUND: Thoracoscopic sympathicotomy (TS) evolved as treatment of choice in severe hyperhidrosis. The aim of this study was to assess the role of video-assistance in TS (VATS) versus conventional TS (CTS) for primary hyperhidrosis of the upper limb with regard to safety, side-effects and long-term outcome. METHODS: 734 TS were performed from below T1 to T4 in 406 patients. In the CTS and in the VATS group 558 and 176 procedures were performed, respectively. Follow-up was completed in 82% of all patients after a median observation period of 16 years. RESULTS: Dry limbs were immediately achieved in 92% (CTS) and 97% (VATS, p = 0.98). Only one patient (CTS) underwent conversion due to bleeding. In the CTS group Horner's syndrome occurred in 2.2% and rhinitis in 9.9% of procedures. No patient of the VATS group experienced Horner's syndrome (p = 0.025), 3 patients developed rhinitis (p = 0.11). At follow-up compensatory sweating was observed in 67.6% vs. 55.6% (p = 0.051) and gustatory sweating in 50.4% and 33.3% (p = 0.01). There were 5 failures or recurrences (1.9%) in the CTS group and 2 (2.8; p > 0.05) in the VATS group at reevaluation. Overall 6.5% (CTS) and 5.6% (VATS) of patients regret the operation (p = 0.7). CONCLUSIONS: We observed a significant decrease of the incidence of complete or incomplete Horner's syndrome and gustatory sweating when the procedure was guided by video-imaging while success rate was similar when compared with CTS.

[Thread design of screw-in acetabulum prostheses]. / Gewindedesign von Schraubpfannen.

INTRODUCTION AND AIM OF STUDY: The screw-in behaviour and correct positioning of threaded cups is largely determined by the design of the thread. Up to now the various thread designs have not been systematically classified. METHODS: The thread designs of 10 first generation and 27 second generation threaded cups were analyzed using a tool setter and a no-touch light section technique. The following parameters were evaluated: thread shape, pitch, number of turns, rows of teeth, tooth length and shape. RESULTS: Threads of the first generation were V-cut or saw shaped. Thread depth was 3.1 mm on average; the mean width was 0.9-3 mm. Single-thread patterns predominated. The number of turns ranged from 1-7; the pitch was from 2.5-5 mm (single thread), or up to 20 mm (triple and quadruple threads). Cups had 3-16 rows of teeth. Threads of the second generation are V-cut, saw or flat shaped. Thread depth is 3 mm on average; mean width ranges from 0.3-2.2 mm. 72% of the threads have single-thread patterns. The number of turns ranges from 2-5; the pitch is from 2.5-6.2 mm (single thread). Cups have 4-24 rows of teeth. CONCLUSIONS: There are many different thread patterns with widely varying parameters. Contemporary threaded cups have a narrow V-cut and saw shaped threads or flat thread with depths up to 3 mm, no more than 5 turns, and pitch values of approx. 4.5 mm.

Development of stable cell lines for production or regulated expression using matrix attachment regions.

One of the major hurdles of isolating stable, inducible or constitutive high-level producer cell lines is the time-consuming selection procedure. Given the variation in the expression levels of the same construct in individual clones, hundreds of clones must be isolated and tested to identify one or more with the desired characteristics. Various boundary elements (BEs), matrix attachment regions, and locus control regions (LCRs) were screened for their ability to augment the expression of heterologous genes in Chinese hamster ovary (CHO) cells. Of the chromatin elements assayed, the chicken lysozyme matrix-attachment region (MAR) was the only element to significantly increase stable reporter expression. We found that the use of the MAR increases the proportion of high-producing clones, thus reducing the number of clones that need to be screened. These benefits are observed both for constructs with MARs flanking the transgene expression cassette, as well as when constructs are co-transfected with the MAR on a separate plasmid. Moreover, the MAR was co-transfected with a multicomponent regulatable beta-galactosidase expression system in C2C12 cells and several clones exhibiting regulated expression were identified. Hence, MARs are useful in the development of stable cell lines for production or regulated expression.

Fitness effects of advantageous mutations in evolving Escherichia coli populations.

The central role of beneficial mutations for adaptive processes in natural populations is well established. Thus, there has been a long-standing interest to study the nature of beneficial mutations. Their low frequency, however, has made this class of mutations almost inaccessible for systematic studies. In the absence of experimental data, the distribution of the fitness effects of beneficial mutations was assumed to resemble that of deleterious mutations. For an experimental proof of this assumption, we used a novel marker system to trace adaptive events in an evolving Escherichia coli culture and to determine the selective advantage of those beneficial mutations. Ten parallel cultures were propagated for about 1,000 generations by serial transfer, and 66 adaptive events were identified. From this data set, we estimate the rate of beneficial mutations to be 4 x 10(-9) per cell and generation. Consistent with an exponential distribution of the fitness effects, we observed a large fraction of advantageous mutations with a small effect and only few with large effect. The mean selection coefficient of advantageous mutations in our experiment was 0.02.