A large population study to assess the magnitude of prenatal programming in dairy cattle.

The performance of an adult dairy cow may be influenced by events that occur before her birth. The present study investigated potential effects of 2 prenatal groups of factors, Assisted Reproductive Techniques (ART) and maternal characteristics (e.g., dam parity), on offspring performance during their first lactation, in populations of 2 dairy cow breeds: French Holstein and Montbéliarde. The different ART studied included the type of semen (conventional or X-sorted) used for Artificial Insemination (AI) and the technology of conception used (AI, embryo transfer, or in vitro fertilization). Three maternal characteristics were considered: (1) the dam age at first calving, (2) dam parity number, and (3) indicators of dam udder health during gestation (somatic cell score and events of clinical mastitis). First, we investigated whether heifer survival from 3d to 18 mo old was associated with any of the prenatal factors considered. We then estimated the associations of these prenatal factors with 8 traits of commercial interest: (1) stature, (2-4) milk, fat, and protein yields, (5) somatic cell score, (6) clinical mastitis, and (7-8) heifer and cow conception rate, all measured on genotyped cows. Linear models were used for this study with the prenatal factors as covariates in the model, and for the 8 traits, phenotypes were adjusted for their corresponding genomic estimated breeding value. The results indicated that the survival rate of heifers born from embryo transfer was significantly higher than that of heifers born from AI (probably due to preferential management practices), while the other prenatal factors did not explain differences in heifer survival. Among the Montbéliarde cows born from AI, those born from X-sorted semen showed a lightly but significantly lower milk yield than those born without X-sorting of the semen (-52 kg of milk in the first lactation). Among the Holstein cows, those born from embryo transfer presented significantly lower milk performance than cows born from AI. Regarding the maternal characteristics, none or very weak associations were found between the dam age at first calving and the offspring performance in both breeds. Dam parity, on the other hand, was associated with offspring performance for milk, fat, and protein yield in both breeds, however not in the same direction. In the Holstein breed, an increase in dam parity was favorable for offspring performance for milk, fat, and protein yield, whereas in the Montbéliarde breed, an increase in dam parity was associated with lower milk and protein yield and no association was found for fat yield. The udder health of the dam during gestation was not or only weakly associated with the traits studied in the offspring. Although some significant associations were identified due to the large sample size, the effects were modest, typically less than 1% of the phenotypic mean, and were not consistently observed across the 2 breeds.

Effects of micronutrient supplementation on performance and epigenetic status in dairy cows.

The postpartum period is crucial in dairy cows and is marked by major physiological and metabolic changes that affect milk production, immune response and fertility. Nutrition remains the most important lever for limiting the negative energy balance and its consequences on general health status in highly selected dairy cows. In order to analyze the effect of a commercial micronutrient on intrinsic parameters, performances and the epigenome of dairy cows, 2 groups of 12 Holstein cows were used: 1 fed a standard diet (mainly composed of corn silage, soybean meal and non-mineral supplement) and the other 1 fed the same diet supplemented with the commercial micronutrient (µ-nutrient supplementation) for 4 weeks before calving and 8 weeks thereafter. Milk production and composition, BW, body condition score (BCS), DM intake (DMI) and health (calving score, metritis and mastitis) were recorded over the study period. Milk samples were collected on D15 and D60 post-calving for analyses of casein, Na+ and K+ contents and metalloprotease activity. Milk leukocytes and milk mammary epithelial cells (mMECs) were purified and counted. The viability of mMECs was assessed, together with their activity, through an analysis of gene expression. At the same time points, peripheral blood mononuclear cells (PBMCs) were purified and counted. Using genomic DNA extracted from PBMCs, mMECs and milk leukocytes, we assessed global DNA methylation (Me-CCGG) to evaluate the epigenetic imprinting associated with the µ-nutrient-supplemented diet. The µ-nutrient supplementation increased BCS and BW without modifying DMI or milk yield and composition. It also improved calving condition, reducing the time interval between calving and first service. Each easily collectable cell type displayed a specific pattern of Me-CCGG with only subtle changes associated with lactation stages in PBMCs. In conclusion, the response to the µ-nutrient supplementation improved the body condition without alteration of global epigenetic status in dairy cows.

Characterization of a new electrostatic storage ring for photofragmentation experiments.

We describe the design of and the first commissioning experiments with a newly constructed electrostatic storage ring named SAPHIRA (Storage Ring in Aarhus for PHoton-Ion Reaction Analysis). With an intense beam of Cu(-) at 4 keV, the storage ring is characterized in terms of the stored ion beam decay rate, the longitudinal spreading of an injected ion bunch, as well as the direct measurements of the transverse spatial distributions under different conditions of storage. The ion storage stability in SAPHIRA was investigated systematically in a selected region of its electrical configuration space.

Photoresponse of the protonated Schiff-base retinal chromophore in the gas phase.

The fragmentation, initiated by photoexcitation as well as collisionally-induced excitation, of several retinal chromophores was studied in the gas phase. The chromophore in the protonated Schiff-base form (RPSB), essential for mammalian vision, shows a remarkably selective photoresponse. The selectivity of the gas-phase chromophore is triggered by a series of fast trans to cis isomerizations followed by a Diels-Alder cyclization with subsequent slow statistical fragmentation, leading to one specific fragment ion. The pattern of the final statistical fragmentation may be altered by chemical modifications of the chromophore. We propose that isomerizations play an important role in the photoresponse of gas-phase retinal chromophores and guide internal conversion through conical intersections. The role of protein interactions is then to control the specificity of the photoisomerization in the primary step of vision and possibly to diminish thermal noise by suppressing spontaneous isomerization by heat.

The treatment of the proximal humeral fracture with the use of the PHN Nailing System: the importance of reduction.

PURPOSE OF THE STUDY: Intramedullary nailing is a minimally invasive technique that respects humeral head. However, limited surgical approach does not permit an anatomical reduction. The significance of the reduction on the functional outcome has not been sufficiently investigated. The aim of the study was to examine the functional and radiological postoperative outcome in patients with proximal humeral fractures treated with intramedullary nailing and the significance of reduction. MATERIALS AND METHODS: The study population consisted of 43 patients with proximal humeral fractures that were treated with the Proximal Humerus Nail System (Targon, Aesculap). Mean follow-up period was 23.2 months (SD: 8.9). Shoulder function was assessed with the Constant-Murley Score. Reduction was examined radiographically anteroposterior and true lateral plane. Radiographs of 50 healthy shoulders served as controls. Malreduction was analyzed for 10°, 15° and 20° in both planes. RESULTS: The overall functional results were satisfying; mean CS of all patients at the last follow-up visit was 74.8 (SD: 19.3). Mean normalized CS for age and gender was 78.15 (SD 17.8). Fracture severity seemed to affect clinical outcome to a certain extent; 4-part fractures exhibited inferior results. Mean NSA was 126.5 (SD: 16.9) in anteroposterio and 137.4 (SD: 15.4) in true lateral view. The respective values in the control group were 134.1° (SD 7.1°) in anteroposterior and 133.7° (SD 12.8°) in true lateral view. A malreduction of >20° in the anteroposterior plane and >15° in both anteroposterior and true lateral planes resulted in significantly inferior clinical outcome. Thirteen complications were recorded, four of them being major. DISCUSSION The quality of reduction affected the postoperative outcome to a certain extent. Especially the anteroposterior reduction seemed to play a more important role in the postoperative function than reduction in the true lateral plane. However, this difference was statistically significant only after > 20° malreduction. The worst results in Constant Score were shown, as expected, in the group with malreduction in both planes; even a 15°malreduction resulted in statistically significant difference. The importance of anteroposterior reduction could be due to achievement of better ROM in the frontal plane, most probably because of better levers on the tuberosities. However an absolute anatomical reduction does not have to be achieved at all costs. The overall good results of the fractures in this study despite absence of anatomical reduction could partly result from the limited surgical approach. CONCLUSIONS: The majority of the patients treated with closed reduction and internal fixation with PHN show good postoperative functional results. However, fracture malreduction reduction cannot be always avoided with the use of PHN. Nevertheless, the evaluation of the Constant-Murley score shows an absolute anatomical reduction in not necessary for satisfying functional outcome. The reduction in anteroposterior plane seems to play a more important role in the postsurgical functional outcome. A malreduction that exceeds 15° in both planes or a malreduction of more than 20° in either plane should be avoided.

The Orthopilot navigation system for primary Bicontact total hip replacement.

AIM: Navigated implantation of the cup and stem components enables additional parameters to be recorded for joint reconstruction. The results and reproducibility of the implant position were studied in a consecutive series of implantations with femoral transmitter (femoral C-clamp) close to the hip joint. METHOD: 107 consecutive cementless THA operations with the Orthopilot Software THA 2.0 were analysed. The preoperative planning for cup and stem position were compared with the intraoperative data from the navigation system and the postoperative radiograph. Cup inclination and anteversion, leg lengths and offset changes and the rotation position of the Bicontact stem were investigated. RESULTS: 98 % of the radiological cup positions were within 42.5 +/- 10 degrees inclination and all cases were within 10 +/- 10 degrees anteversion. The navigation system recorded 83 % of the relative leg length changes with an accuracy of +/- 5 mm. 15 % were in a range of +/- 10 mm. In 77 % of the operations, the Bicontact stem or the Bicontact B osteoprofiler could be positioned in the position measured by the Orthopilot of +/- 5 degrees of the box osteotome (i.e. medullary cavity opening). In 20 % the deviation was +/- 10 degrees . 73 % of the arthroplasties gave a relative offset change in a range of +/- 10 mm. A tendency to medialisation of the hip joint centre was seen in 62 % of the procedures. The mean was a small offset change of only 1.2 mm with a high standard deviation of 17.8 mm. CONCLUSION: The navigated implantation of stem and cup components with a femoral transmitter close to the joint leads to reproducible results. The distribution of femoral offset and leg length changes corresponds to clinical experience. Analysis of the radiographs does not appear sufficiently accurate for all the recorded parameters.

The use of a bronchial blocker compared with a double-lumen tube for single-lung ventilation during minimally invasive direct coronary artery bypass surgery.

OBJECTIVE: To investigate whether a bronchial blocker (BB) placed through a routinely used single-lumen tube (SLT) to achieve 1-lung ventilation is appropriate in patients undergoing a minimally invasive direct coronary artery bypass (MIDCAB) operation. DESIGN: Clinical trial. SETTING: University hospital. PARTICIPANTS: Patients scheduled for elective MIDCAB operation (n = 159). INTERVENTIONS: Group A was treated with a left-sided double-lumen tube (DLT) and served as the control group. Group B was intubated with a routinely used SLT in combination with a BB. MEASUREMENTS AND MAIN RESULTS: The following data were collected: (1) time required for placement of each tube, (2) ventilation pressures, (3) lung compliance, (4) dislocations of the DLT or BB, (5) effectiveness of lung collapse, and (6) PaO(2) and fraction of inspired oxygen. In 4 patients (4%) of group B, the BB could not be placed within an acceptable time so that 155 patients (50 patients in group A, 105 patients in group B) were statistically analyzed. Statistically significant differences during 1-lung ventilation were found for peak and mean inspiratory pressure (p < 0.001 and p < 0.05), dynamic and static lung compliance (p < 0.05), and dynamic lung compliance change (p < 0.01). No statistical significance was found for intubation time (p > 0.05) and PaO(2) and fraction of inspired oxygen (p > 0.05). Lung collapse was insufficient in 1 patient of group A (2%) and in 2 patients of group B (2%). CONCLUSION: To achieve 1-lung ventilation during a MIDCAB procedure, the use of a BB combined with an SLT is an appropriate technique as an alternative to the commonly used DLT.

Quantitative effects on gene silencing by allelic variation at a tetranucleotide microsatellite.

Microsatellites are common repeated sequences, which are useful as genetic markers and lack any clearly established function. In a previous study we suggested that an intronic polymorphic TCAT repeat in the tyrosine hydroxylase (TH) gene, the microsatellite HUMTH01, may regulate transcription. The TH gene encodes the rate-limiting enzyme in the synthesis of catecholamines, and the microsatellite HUMTH01 has been used in genetic studies of neuropsychiatric and cardiovascular diseases, in which disturbances of catecholaminergic neurotransmission have been implicated. HUMTH01 alleles associated with these diseases act as transcriptional enhancers when linked to a minimal promoter and are recognized by specific nuclear factors. Here we show that allelic variations of HUMTH01 commonly found in humans have a quantitative silencing effect on TH gene expression. Two specific proteins, ZNF191, a zinc finger protein, and HBP1, an HMG box transcription factor, which bind the TCAT motif, were then cloned. Finally, allelic variations of HUMTH01 correlate with quantitative and qualitative changes in the binding by ZNF191. Thus, this repeated sequence may contribute to the control of expression of quantitative genetic traits. As the HUMTH01 core motif is ubiquitous in the genome, this phenomenon may be relevant to the quantitative expression of many genes in addition to TH.

Arthroscopic reduction and internal fixation (ARIF) of lateral tibial plateau fractures.

Arthroscopic reduction and internal fixation of tibial plateau fractures has been well documented over the last 15 years. Better visualization, less traumatic surgery, reconstruction of accompanying injuries and early mobilization have encouraged arthroscopic surgeons to use this technique more widely. With experience, surgeons became more comfortable in using arthroscopy-assisted surgery not only in split fractures of the lateral tibial plateau (41-B1) but also in more complex tibial and femoral fractures. In this study, 31 patients with intra-articular fractures of the lateral tibial plateau were operated on between 1991 and 1996. The fractures were classified as follows: x12 AO-type B1, x7 B2, x10 B3, x2 C3. Diagnostic arthroscopy and repair of soft tissue injuries was followed by arthroscopic reduction in all patients and supplemented with internal fixation in 29 patients. Postoperatively, an aggressive physical therapy regimen was performed with immediate mobilization and early partial weight bearing. All patients were examined for follow-up after 15-32 months (mean 25.1). In all cases the fractures were stable and allowed full weight-bearing. At follow-up, 25 patients had anatomic reduction. Anatomical reduction cannot be restored in all cases of open reconstruction because of cartilage defects. Fracture reduction using arthroscopic techniques is a suitable alternative for joint fracture repair because additional soft tissue damage can be minimized.

[Arthroscopically-assisted reconstruction of the anterior cruciate ligament with autologous patellar tendon replacement-plasty. 5 years results]. / Die arthroskopisch gestützte Rekonstruktion des vorderen Kreuzbands mittels autologer Patellarsehnenersatzplastik. 5-Jahres-Ergebnisse.

This study presents the five-year follow-up-results (range 56 to 63 months) of 76 of 119 patients who had had arthroscopically assisted reconstruction of the anterior cruciate ligament with use of the central third patellar tendon for acute rupture (19 patients = group A) or chronic ACL insufficiency (57 patients = group B) between may 1991 and october 1993 in the Department of Trauma Surgery University Hospital Ulm. The average Lysholm knee score was 94.6 points (group A = 97.1, group B = 93.8 points). The IKDC-score rated 21.1% of all patients as A (group A = 31.6%, group B = 17.5%), 57.9% as B (group A = 52.6%, group B = 59.6%), 19.7% as C (group A = 15.8%, group B 21.7%) and one patient of group B as level D. 9 patients (= 11.8%, group A = 21.1%, group B = 8.8%) showed up to 10 degree extension loss (compared with contralateral knee), one patient of group A (1.3%) more than 10 degree. A flexion loss up to 15 degree was seen in 12 patients (= 15.8%, group A = 21.1%, group B = 14.0%), of more than 15 degree in 3 patients (= 3.9%, group A = 5.3%, group B = 3.5%). The average KT-1000-side-to-side difference was 2.5 mm with 90 N (group A 2.4 mm, group B = 2.5 mm), 2.8 mm with 133 N (group A = 2.7 mm, group B = 2.8 mm) and 3.2 mm (both groups) for manual maximum. There was no statistically significant difference in quadriceps and hamstring isokinetic strength (Cybex) of operated vs. unaffected limb for 60/s as well as 240/s. X-ray analysis showed arthrotic signs of minimum one compartment in 22.3% of all patients (group A = 26.3%, group B = 21.1%). In summary, we found better long-term results of IKDC-score in patients with autogenous patellar tendon graft for acute ACL-rupture vs. chronic ACL insufficiency. In Lysholm knee score and KT-1000 arthrometric measurement we just saw little but not statistically significant differences between the two groups. The isokinetic strength of quadriceps and hamstring were similar between operated vs. unaffected limb as well as between group A and B.

Bacterial expression of G-protein-coupled receptors: prediction of expression levels from sequence.

Eleven G-protein-coupled receptors were expressed in Escherichia coli as fusion proteins with N-terminal glutathione-S-transferase and a C-terminal (His)6 tag. Expression levels varied between 0.1% and 10% of the total cellular protein. Low expression levels, as quantified by analytical nickel chelating chromatography, coincided with a toxic effect of protein expression. Multiple linear regression analysis was used to establish a correlation between the occurrence of positively charged amino acid residues in the loop regions and the expression level. Indeed, 44% of the variation in expression levels could be attributed to the positive charge content. Consequently, this sequence feature is the major determinant of expression level. Our results were supported by two mutations where positive charges were introduced into loop regions of two low-expressing receptors: As predicted, these mutations led to a considerably higher expression. A similar mutation of an olfactory receptor described previously increased expression approximately 100-fold and further supports our model. The data are discussed in the context of the "positive inside rule".

Influence of etiology in heterotopic bone formation of the hip.

OBJECTIVE: Heterotopic ossification (HO) in periarticular tissue can appear after brain or local joint trauma. The aim of this study was to investigate differences of manifestation and outcome after surgical therapy of patients suffering from HO of the hip after isolated brain injury (n = 18), local hip trauma (n = 21), or the combination of both (n = 25). HO can cause progressive lost of joint movement; once mature, the only therapy to improve joint mobility is the excision. METHODS: All patients underwent surgical removal of HO and postoperative irradiation therapy. On the basis of plain radiographic findings, we evaluated the recurrent ossification after 1-year and 5-year follow-up periods. Within this prospective study, clinical performance status was scored according to the classification of d'Aubigne and a planimeter was used to evaluate the area of heterotopic bone formation in standard x-rays films. RESULTS: The severity of brain trauma observed by Glasgow Coma Scale correlated with the ossification size (square centimeters). Correlation was noticed as well between severity of brain injury and functional outcome. The evaluation of an average 1-year and 5-year follow-up period showed relief of pain and clear improvement of range of motion in all patients. There was mild recurrence of heterotopic bone growth within the first postoperative year without deterioration of the functional results. CONCLUSION: The severity of brain trauma has an influence on the extent of HO near the hip joint and also on the rehabilitation process. The histologic findings and recurrence of HO after excision were not affected by the localization of initial trauma. There was only mild recurrence of heterotopic bone growth between the first and fifth postoperative year. For objective evaluation of heterotopic bone formation in standard x- ray films, planimetric measurement is a useful method.

Distant downstream sequence determinants can control N-tail translocation during protein insertion into the endoplasmic reticulum membrane.

We have studied the membrane insertion of ProW, an Escherichia coli inner membrane protein with seven transmembrane segments and a large periplasmic N-terminal tail, into endoplasmic reticulum (ER)-derived dog pancreas microsomes. Strikingly, significant levels of N-tail translocation is seen only when a minimum of four of the transmembrane segments are present; for constructs with fewer transmembrane segments, the N-tail remains mostly nontranslocated and the majority of the molecules adopt an "inverted" topology where normally nontranslocated parts are translocated and vice versa. N-tail translocation can also be promoted by shortening of the N-tail and by the addition of positively charged residues immediately downstream of the first trasnmembrane segment. We conclude that as many as four consecutive transmembrane segments may be collectively involved in determining membrane protein topology in the ER and that the effects of downstream sequence determinants may vary depending on the size and charge of the N-tail. We also provide evidence to suggest that the ProW N-tail is translocated across the ER membrane in a C-to-N-terminal direction.

[Simultaneous transarticular intramedullary nailing of the tibia and total knee replacement in tibial nonunion and osteoarthrosis]. / Transartikuläre Tibianagelung und simultaner Kniegelenkersatz bei Tibiapseudarthrose und Gonarthrose.

The combined manifestation of a nonunion of the proximal tibia and an osteoarthrosis of both knee joints is not very common. Yet, this was a kind of "unhappy triad" for a 86 year old lady suffering from a nonunion after one year of conservative treatment of a proximal tibial shaft fracture. Her quality of life has already been reduced by a loss of visual power and she was completely invalidized. She was unable to walk and she was hospitalized for the whole period of time. The operative treatment consisted in an intramedullary tibial nailing through the resected tibial joint surface using an IMSC-nail and, simultaneously through the same surgical approach, in a partially cemented total knee joint replacement. After 5 months a replacement of the second knee joint also was performed and 6 weeks later the almost blind patient could be discharged for home again. After another 7 months a proximal femoral fracture of the first side was repaired using a proximal femural nail. Four years later she still is able to live on her own and runs her flat with only little external help. She can walk as far as 3 km and enjoys a good knee function.

Neuron-restrictive silencer elements mediate neuron specificity of adenoviral gene expression.

Neuron-restrictive silencer elements (NRSEs) were used to target the gene expression of adenoviral vectors specifically to neuron cells in the central nervous system. By generating adenoviral constructs in which NRSE sequences were placed upstream from the ubiquitous phosphoglycerate kinase promoter, the specificity of expression of a luciferase reporter gene was tested in both cell lines and primary cultures. Whereas transgene expression was negligible in nonneuronal cells following infection with an adenovirus containing 12 NRSEs, neuronal cells strongly expressed luciferase when infected with the same adenovirus. The NRSEs restricted expression of the luciferase gene to neuronal cells in vivo when adenoviruses were injected both intramuscularly into mice and intracerebrally into rats. This NRSE strategy may avoid side effects resulting from the ectopic expression of therapeutic genes in the treatment of neurological diseases. In particular, it may allow the direct transfection of motor neurons without promoting transgene expression within inoculated muscles or the secretion of transgene products into the bloodstream.

[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS]. / Lipid-Intervention und koronare Herzkrankheit bei Männern unter 56 Jahren. Die Coronare Interventions-Studie: CIS.

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

Clinical experience with PDS II augmentation for operative treatment of acute proximal ACL ruptures--2-year follow-up.

The results of prospective anterior cruciate ligament (ACL) refixation in 33 patients with high proximal rupture is reported at 20-28 months' follow-up: mean age was 31.1 +/- 12.5 years. The surgical technique was a specially developed refixation of the ACL using a multiple suture loop (modified Marshall technique) augmented with intra-articular PDS II (polydioxanon, resorbable, Ethicon, Hamburg, Germany) to avoid derangement of blood circulation and to guarantee early functional rehabilitation. All patients were operated on within 7.3 +/- 4.5 days after injury. According to the IKDC evaluation score, 22 patients showed excellent and 10 patients good subjective function. Twenty regained their pre-injury level of activity. Anterior stability was tested manually and by KT-1000 max (Medmetric, San Diego). Twenty-eight patients had a firm end-point, although there was a positive Lachman test in 16 patients. Maximal joint laxity as measured by KT-1000 showed a 1-2 mm, 3-5 mm, 6-10 mm and > 10 mm anterior drawer for 16, 14, 2 and 1 patients, respectively. Twenty-five of the evaluated knee joints had a negative pivot shift test. Three patients had a limited range of motion. The potential advantages of PDS II-augmented refixation of acute proximal ACL ruptures are anatomic reconstruction without destruction of other anatomic structures used as grafts, early functional rehabilitation and possibly better proprioception.

[Augmentation techniques: are they out?]. / Augmentationstechniken: Sind sie out?

UNLABELLED: Basics of ligament augmentation are reviewed from the literature. As biomechanical in-vitro studies, animal experiments, and clinical studies show different designs and data, the results may be interpreted variably. Theoretically there is a positive effect of augmentation, but no significant improvement of clinical results is evident. The goal of our own prospective study was to check the healing capacity of a repaired and augmented ACL with respect to stability compared to a primary or secondary BTB ligament replacement with and without augmentation. 200 patients were allocated to 4 groups. In group I (G1) acute proximal ruptures were repaired arthroscopically and augmented with PDS II-cord. Patients in G2 received an acute and in G3 a late BTB ligament replacement. Additionally in G4 a late ligament replacement was augmented with a PDS II-cord. The clinical results reveal a comparative stability between G1 and G2, and gradually less stability in G3 and G4. Subjectively, knee function was felt best in G1 and G2 while being worst in G3 and G4. There is no significant difference in the mobility of knees between primary and secondary ligament replacement. An additional augmentation doesn't improve the knee stability. CLINICAL RELEVANCE: There is no positive effect of an augmentation technique of a biologic ligament replacement concerning stability, morbidity, complication rate, and costs. Very marginal freshly ruptured cruciate ligaments may be reinserted successfully by a biodegradable augmentation. Subjective feeling and functional stability may be at least equal to a primary ligament replacement. There are no advantages in knee mobility, when a secondary ligament replacement is performed.

Acceleration of lpr lymphoproliferative and autoimmune disease by transgenic protein kinase CK2 alpha.

MRL-lpr/lpr mice have a Fas receptor mutation that leads to abnormalities of apoptosis, lymphoproliferation, and a lupus-like autoimmune disease associated with the production of autoantibodies. Other than Fas pathway defects, little is known about molecular abnormalities that predispose to autoimmunity. Protein kinase CK2 (also termed casein kinase II), a serine-threonine protein kinase whose targets include many critical regulators of cellular growth, is highly expressed in a lymphoproliferative disease of cattle and in many human cancers. Overexpression of the CK2alpha catalytic subunit in lymphocytes of transgenic mice leads to T cell lymphoma. We hypothesized that CK2 dysregulation and Fas mutation might cooperatively augment lymphocyte proliferation and transformation. We find that in MRL-lpr/lpr mice bearing the CK2alpha transgene, the lymphoproliferative process is dramatically exacerbated, as these mice develop massive splenomegaly and lymphadenopathy by 12 wk of age in association with increased autoantibody production and accelerated renal disease. The lymphoid organs are filled with the unusual B220+CD4-CD8- T cells typically seen in MRL-lpr/lpr mice, not the B220-CD4+CD8+ or B220-CD4-CD8+ T cells typically seen in CK2a transgenic lymphomas. The T cells do not fulfill the criteria for transformation, as they are polyclonal and not transplantable or immortal in cell culture. Thus, although the lpr lymphoproliferative and autoimmune syndrome is potentiated by the presence of the CK2a transgene, this combination of apoptotic and proliferative abnormalities appears to be insufficient to transform lymphoid cells.