Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction.

OBJECTIVE: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. METHODS: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. RESULTS: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. CONCLUSIONS: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

Sheep and goats: separating cervix and corpus uteri from imprecisely coded uterine cancer deaths, for studies of geographical and temporal variations in mortality.

Analysing time trends in mortality from cancers of the cervix and corpus uteri using routine data sources (such as the World Health Organisation mortality database) involves two major problems: deaths certified as "uterus, unspecified site", and the presence of a combined category comprising unspecified and corpus uteri cancer deaths. To avoid misleading interpretations, the unspecified and the misclassified data must be incorporated into the analysis to produce rates that allow meaningful comparisons between populations and over time. Reallocation methods based on age- and time-specific distributions of cervix and corpus uteri cancer are applied to the unspecified deaths, while for those in the combined category, the age- and time-specific distributions of unspecified and corpus uteri cancer are considered. Adjustments of the general strategies for reallocation were developed to take into account the different quality of the data. Results from eight European countries with different degrees of coding precision are presented. The reallocation methods bring the cervix and corpus uteri mortality trends more in line with the trends for countries with more precise data while keeping the country-specific characteristics. In addition, the methods ensured the availability of time trends for corpus uteri cancer in women age 50 years and older, which were completely missing without reallocation. We propose generally applicable reallocation methods that allow valid time trend analysis of cervix and corpus uteri cancer mortality using datasets of varying precision. Our results show that any sensible analysis of time trends must involve procedures for correcting for unspecified and misclassified uterine cancer deaths. The modified data are available at .

Risk factors influencing the outcome after surgical treatment of complicated deep sternal wound complications.

BACKGROUND: Median sternotomy is the most frequently used incision for cardiac procedures but carries a substantial risk for deep sternal wound infections and/or sternal dehiscence. In contrast to previous studies that examined risk factors for sternal infections this study evaluates factors that lead to poor outcome after surgical revision of the non healing sternum. METHODS: Between 1985 and 1999, 193 adults (mean age 64 +/- 9 years, m/f = 3/1) necessitated sternal revisions (incidence 1.93%). Pre-, intra- and post-operative risk factors were evaluated for their influence on the outcome after sternal revision. RESULTS: 65 of the 193 patients had a complicated course: ten (5.2%) died due to sepsis/multi organ failure (n = 6) or cardiac causes (n = 4). 32 patients (16.6%) needed several revisions, 17 (9%) were discharged with sternal instability, 5 (3%) with chronic fistula and one with persistent osteomyelitis. Univariate and multivariate analysis identified cardiopulmonary resuscitation (odds ratio (OR) = 11.188, p = 0.010), corticoid treatment (OR = 7.043, p = 0.0055), diabetes (OR = 4.130, p = 0.0128), smoking history (OR = 2.996, p = 0.0041), renal insufficiency (hazard ratio (HR) = 1.884), old age (OR = 1.108, p = 0.0266), high body mass (HR = 1.06), ECC time (p = 0.023), cross clamp time (p = 0.028), systemic hypothermia (p = 0.016), non-use of IMA (p = 0.042) or prolonged ventilation as risk factors for mortality or poor outcome. No correlation between sternal closure technique, mediastinal irrigation or antibiotic therapy and outcome after mediastinal revision could be found. CONCLUSIONS: To avoid disappointing results after sternal revision one should aim to preoperatively identify high-risk patients and aggressively address risk factors. This rather than modifications of the surgical and medical approach might improve the outcome of patients with mediastinal complications.

[Coronary revascularization: off-pump versus on-pump--a comparison of behavior of biochemical cardiac ischemia markers]. / Koronarrevaskularisation: Off-pump versus On-pump--Verhalten der biochemischen kardialen Ischämiemarker im Vergleich.

BACKGROUND: Recently, coronary artery bypass grafting (CABG) on the beating heart with avoidance of extracorporeal circulation (off-pump CABG technique) has been gaining increasing importance in modern cardiac surgery. The object of this prospective study was to compare postoperative kinetic and patterns of cardiac troponin I (cTnI), T (cTnT), and creatine kinase MB (CKMB) activities after off-pump CABG versus conventional on-pump CABG. METHODS: We studied 106 patients who underwent first-time elective on-pump (group I, n = 69, 56 male, 13 female, mean age: 64.3 +/- 9.9 years, mean ejection fraction: 56 +/- 15%) or off-pump (group II, n = 37, 24 male, 13 female, mean age: 68.4 +/- 9.1 years, mean ejection fraction: 57 +/- 13%) CABG surgery via median sternotomy. CTn I and cTnT levels, total creatine kinase (CK) and CK-MB activities in the serum were measured before operation, up on arrival at the ICU and 6, 12, 24, 48 and 120 hours later. Serial 12-lead ECGs were recorded preoperatively and on days 1, 2 and 5. RESULTS: Serum concentrations of cardiac troponins in all patients were preoperatively either not detectable or in the normal range and significantly increased after surgery. In group I, one patient developed a Q wave myocardial infarction, one patient a non-Q wave infarction and two patients a new left bundle branch block on the ECG. One patient of group II developed a new Q-wave myocardial infarction and another patient permanent atrial fibrillation associated with a continuous arrhythmia. All patients with a myocardial infarction in the ECG showed significant elevation of concentrations or activities of these biochemical markers. The median postoperative peak values for cTnI were measured at 24 h in both groups (2.7 micrograms/l, 95%-CI: [2.2, 3.2] in group I and 1.1 micrograms/l, 95%-CI: [0.5, 1.3] in group II). CTnT postoperatively presented an earlier median peak of 0.128 microgram/l at 12 h in group II (95%-CI: [0.041, 0.146]) than in group I at 48 h (0.298 microgram/l, 95%-CI: [0.254, 0.335]). CONCLUSIONS: All patients undergoing CABG surgery with or without extracorporeal circulation postoperatively showed an increase of cardiac troponin levels. After uncomplicated coronary revascularization, patients with the off-pump CABG technique continuously presented lower serum cardiac troponin concentrations than those with the on-pump CABG technique. CTnI showed the same patterns of release in both groups with different median postoperative peak values at 24 h. The patterns off cTnT release following CABC surgery with or without extracorporal circulation were different: CTnT reaches its postoperative peak value in patients with the off-pump CABG technique earlier than those with the on-pump CABG technique (12 h postoperatively versus 48 h).

Patterns and diagnostic value of cardiac troponin I vs. troponin T and CKMB after OPCAB surgery.

BACKGROUND: Cardiac troponin I (cTnI) has been shown to be a specific marker for myocardial injury in cardiac surgery. The object of this prospective study was to determine the patterns and kinetic and diagnostic value of cTnI, cardiac troponin T (cTnT), and creatine kinase MB (CKMB) activity after minimally invasive coronary revascularization using an octopus device on the beating heart (OPCAB). METHODS: 48 patients (33 male/15 female, mean age 68.3 +/- 8.7 years) underwent their first elective OPCAB surgery with median sternotomy without mortality. The mean number of grafts was 2.0 +/- 0.8 per patient. Preoperative mean ejection fraction was 56.6 % +/- 14.9%. CTnI and T levels, total creatine kinase (CK) and CK-MB activity in the serum were measured before operation, at arrival at the ICU, and 6, 12, 24, 48 and 120 hours afterward. Serial 12-lead ECGs were recorded preoperatively and at days 1, 2 and 5. The relationship between perioperative data and postoperative cTnI and cTnT levels and CKMB were statistically identified for all variables. RESULTS: The best cutoff value for cTnI was 8.35 micrograms/l. The patients were grouped by the ECG findings and maximal slopes of cTnI postoperatively (group I: unchanged ECG and cTnI < 8.35 micrograms/l, n = 38; group II: unchanged ECG and cTnI > 8.35 micrograms/l n = 6; group III: Q-wave in ECG and cTnI > 8.35 micrograms/l, n = 4). Baseline serum concentrations of cTnI were in the normal range, and significantly increased after surgery with a peak 24h after the operation. Maximal slopes of cTnI ranged in group II between 9.1 and 18.0 micrograms/l, and in group III between 35.9 and 88.8 micrograms/l. There was strong concordance between maximum cTnI, cTnT (p < 0.0001) and CK-MB levels (p = 0.003). First cTnI levels immediately post-op correlated with the maximum cTnI levels during the postoperative course (p = 0.009). CONCLUSIONS: CTnI after minimal invasive surgery shows a characteristic pattern with a maximum at 24h after the operation. The measurement of postoperative biochemical marker concentrations, specially cTnI, reflects myocardial injury incurred during the procedure. It is an accurate method for confirming or excluding a perioperative myocardial injury diagnosis after OPCAB surgery.

[IMZ-TwinPlus bone implant system--4 years clinical experience]. / Das IMZ-TwinPlus-Schraubenimplantat-System--4 Jahre klinische Erfahrung.

AIM OF THE STUDY: For more than twenty years the IMZ-system has been in clinical use, since 1995 modified as IMZ-TwinPlus. The aim of this prospective clinical trial was to analyse the success of the latter implant system, which is an automatically threading cylindrical titanium screw with a deep structured surface (Fa. FRIATEC AG, Mannheim, BRD). Investigated parameters were the peri-implant situation of the soft tissues, the bone loss and the rate of implant failure after a maximum period of 4.5 years of clinical use. MATERIAL AND METHODS: From 1995-2000 sixty-eight patients were provided with a total of 278 IMZ TwinPlus screw implants for various indications (mainly alveolar ridge atrophy). 191 implants were inserted without any, 35 implants with a loco-regional and another 52 implants after comprehensive reconstructive osteoplastic surgery. 38 patients with 155 implants were re-examined using a standardised protocol to evaluate peri-implant hard- and soft tissue situation as well as the patient's subjective assessment of the treatment. RESULTS: With a maximum of 54 months the mean observation period was 30 months. The implant failure rate has risen to 6% so far (n = 18 in 12 patients). Two patients bearing 7 implants have passed away. One patient with 4 implants was lost to follow up. 249 implants were still under function at examination, thus the in situ rate was 91%. The Kaplan-Meier survival rate after 54 months proved 91%. DISCUSSION: To our knowledge there are at present no other data published on the survival rate of the IMZ TwinPlus implant system. The results of this study evaluate a survival rate similar to the classical IMZ cylinder implant and other implant systems for the analysed observation period. CONCLUSIONS: After a maximum observation period of 4.5 years the IMZ TwinPlus implant system showed results in the range of other well-established implant systems. Designed to resist rotation of the superstructure the IMZ TwinPlus screw implant widens the range of indications in comparison to the classical IMZ cylinder implant system.

VEGF(165) mediates glomerular endothelial repair.

VEGF(165), the most abundant isoform in man, is an angiogenic cytokine that also regulates vascular permeability. Its function in the renal glomerulus, where it is expressed in visceral epithelial and mesangial cells, is unknown. To assess the role of VEGF(165) in glomerular disease, we administered a novel antagonist - a high-affinity, nuclease-resistant RNA aptamer coupled to 40-kDa polyethylene glycol (PEG) - to normal rats and to rats with mesangioproliferative nephritis, passive Heymann nephritis (PHN), or puromycin aminonucleoside nephrosis (PAN). In normal rats, antagonism of VEGF(165) for 21 days failed to induce glomerular pathology or proteinuria. In rats with mesangioproliferative nephritis, the VEGF(165) aptamer (but not a sequence-scrambled control RNA or PEG alone) led to a reduction of glomerular endothelial regeneration and an increase in endothelial cell death, provoking an 8-fold increase in the frequency of glomerular microaneurysms by day 6. In contrast, early leukocyte influx and the proliferation, activation, and matrix accumulation of mesangial cells were not affected in these rats. In rats with PHN or PAN, administration of the VEGF(165) aptamer did not influence the course of proteinuria using various dosages and administration routes. These data identify VEGF(165) as a factor of central importance for endothelial cell survival and repair in glomerular disease, and point to a potentially novel way to influence the course of glomerular diseases characterized by endothelial cell damage, such as various glomerulonephritides, thrombotic microangiopathies, or renal transplant rejection.

Protein binding regions of the mRNAs for the 55 kDa tumor necrosis factor receptor and the glucose transporter 1: sequence homology and competition for cellular proteins.

Gene expression is influenced by mechanisms regulating mRNA degradation. Knowledge on regulatory RNA elements involved and on proteins interacting with them is still limited. A 33 nucleotide (nt) region of the 55 kDa tumor necrosis factor receptor (TNFR-55) mRNA, previously reported by us to engage in such interaction with proteins from U-937 cells, exhibits homology to a 38 nt regulatory region of the glucose transporter GLUT-1 mRNA. Labeled RNA fragments comprising these two regions bind similar sets of proteins. Upon phorbol ester-induced differentiation into macrophage-like cells, protein binding to both fragments is changed similarly. Furthermore, both compete with each other for protein binding. This suggests that GLUT-1 and TNFR-55 RNA share a novel protein binding RNA motif involved in regulation of their half life.

Detection of 100% of the CFTR mutations in 63 CF families from Tyrol.

We identified 100% of the CFTR gene mutations, including three novel mutations, in 126 unrelated cystic fibrosis chromosomes from Tyrol, Austria. The frequency of the major mutation deltaF508 (74.6%) was not significantly different in Tyrolian CF-patients than in patients from Bavaria (71.0%) and Middle- and Northern Germany (71.9%), but was significantly higher than in patients from Styria (58.1%) or Northern Italy (47.6%). Interestingly, the distribution of the next most frequent mutations, R1162X (8.7%) 2183AA-->G, 2789+5G-->A and G542X (2.4% each), was more similar to the distribution of these mutations among CF-patients from Northern Italy than to those from Styria, Bavaria or Middle- and Northern Germany. Nine further mutations occurred once or twice. One of these, the missense mutation M1101K, is rare worldwide but very frequent in the Hutterite brethren, a small founder population which came from Southern Austria to Northern America. Three other different mutations (deltaL453, 1874insT and 4108delT) were present in single Tyrolian families and have not been described before. The identification of 100% of CFTR gene mutations in a particular CF population demonstrates the power of genetic analysis for the diagnosis and counselling of CF families in this restricted geographical area of Austria. Our study provides evidence for a closer genetic relation between CF patients from Tyrol and those from Bavaria or Middle- and Northern Germany as well as Northern Italy, than between CF patients from the two Austrian states Tyrol and Styria.

[Maternal serum levels of cystine-aminopeptidase (C.A.P.) in normal and pathological pregnancies (author's transl)]. / Etude des taux sériques de cystine-aminopeptidase (C.A.P.) ou ocytocinase dans la grossesse normale et pathologique.

The variations of the maternal serum levels of cystine-aminopeptidase or oxytocinase (C.A.P.) have been studied in 399 measurements from 326 pregnant patients, 226 normal pregnancies were used as control and allowed us to set up a range of normal values for the age of pregnancy; the mean levels increase exponentially. It has not been possible from this study to establish conclusively a direct relationship between the C.A.P. levels, or variations of these levels and the onset of a fetal and/or placental pathology. In twin pregnancies only, the levels were constantly elevated.