Cardiac Risks in Multimodal Breast Cancer Treatment

Strahlentherapie und Onkologie -     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Antioxidant defence during cardiopulmonary bypass surgery.

OBJECTIVE: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation. METHODS: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure. RESULTS: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure. CONCLUSION: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage.     

Endoscopically controlled sinus floor augmentation. A preliminary report.

Sinus augmentation has been advocated to be a surgical technique with predictable results in peri‐implant surgery. Endoscopic surgery of the maxillary sinus so far has been used as diagnostic procedure. In this paper, the use of endoscopy is described as a low invasive adjunctive technique in sinus floor augmentation. After preparation of the mucoperiosteum, bone grafts can be placed under endoscopic control between sinus floor and mucoperiosteum. A laterobasal approach via a small osteotomy and a transalveolar approach are possible for mucosal elevation and graft placement. First clinical results are reported. Endoscopic sinus lift may contribute to a reduction of perioperative morbidity, reduction of oroantal fistulae and control of graft position. The less invasive technique may allow to extend the indication for sinus augmentation.     

Pulmonale Thrombendarterektomie: Die Therapie der chronisch thromboembolischen pulmonalen Hypertension— Initiale chirurgische Erfahrung

Zusammenfassung Grundlagen Die pulmonale Thrombendarterektomie stellt eine effektive Therapie zur Behandlung von Patienten mit chronisch thromboembolischer pulmonalar Hypertonie dar. Wir berichten über unsere Erfahrungen mit dieser Operationstechnik bei den ersten 9 Patienten. Methodik Zwischen 1992 und Oktober 1994 wurde bei 9 Patienten eine pulmonale Thrombendarterektomie durchgeführt. über eine mediane Sternotomie wurden die Pulmonalarterien beider Seiten bis in ihre subsegmentalen Aufzweigungen im Sinne einer echten Endarterektomie vom organisierten thromboembolischen Material befreit. Zumeist waren Perioden des totalen Kreislaufstillstandes in tiefer Hypothermie notwendig, wobei diese zunehmend verkürzt werden konnten und 3 Patienten vollst?ndig ohne Kreislaufstopp operiert wurden. Ergebnisse Die perioperative Mortalit?t betrug 11%, wobei der 1. Patient am 14. postoperativen Tag an den Folgen eines Reperfusions?dems verstarb. Alle anderen Patienten sind 4 bis 22 Monate (im Mittel 13 Monate) nach dem Eingriff am Leben und zeigen eine Hochsignifikante Verbesserung ihrer h?modynamischen Situation (mean PAP pr?operativ: 62 mm Hg, postoperativ: 30 mm Hg p<0,001; Cardiac Index pr?operativ: 2,1 1/min/m², postoperativ: 3,6 l/min/m² p=0,001). W?hrend pr?operativ alle Patienten in NYHA-Klasse III oder IV waren, sind die 8 überlebenden jetzt alle in Klasse I oder II. Schlu?folgerungen Die pulmonale Thrombendarterektomie bietet eine erfolgreiche Therapiem?glichkeit für Patienten mit chronisch thromboembolischer pulmonaler Hypertonie mit einer in Anbetracht fehlender konservativer Altermativen akzeptablen Mortalit?t und ausgezeichneten funktionellen Langzeitergebnissen.      

Placental p,p''-dichlorodiphenyldichloroethylene and cord blood immune markers

Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration.     

Extended donor criteria for lung transplantation--a clinical reality.

OBJECTIVE: Standard lung donor criteria have been established on opinions and individual experiences rather than on existing evidence. Since the scarcity of donor organs is one of the major limitations to lung transplantation, extension of donor lung criteria might considerably increase the donor pool. This study therefore evaluates the outcome, achieved with the use of extended donors versus standard donors and aims to redefine lung donor criteria. METHODS: We performed a retrospective analysis of 98 consecutive primary lung transplantations from 94 donors from 1/2001 to 12/2002. Donors were classified as extended if they fulfilled at least one criteria: age >55 years, PaO(2) at FiO(2)/PEEP 5 <300mmHg, tobacco history >20 pack years, inhalative drug abuse, presence of infiltration on chest X-ray or purulent secretions at bronchoscopy. Recipients were stratified in two groups according to whether they received a 'standard' or 'extended' organ. Postoperative complications, extubation time, ICU and hospital stay and survival were compared. RESULTS: Twenty-three (24.5%) donors were extended. Twenty-six recipients (26.55%) received organs from extended donors. Differences in intubation times (12+/-2 days standard vs. 14+/-5 days extended, P=0.70), ICU stay (16+/-2 days standard vs. 18+/-5 days extended, P=0.74) and hospital stay (38+/-4 days standard vs. 40+/-6 days extended, P=0.71) were not statistically significant. Postoperative bleeding rates were comparable (n=14 standard vs. n=3 extended) as well as bronchial anastomotic complications (n=7 standard vs. n=3 extended). Three months survival was 88.89% in the standard group vs. 92.31% in the extended group. One year survival is comparable as well with 81.94 vs. 84.62%, respectively. CONCLUSIONS: The use of lung donors who fail to meet standard criteria does not impair short and medium term results compared to standard lung donors. The impact on long term development of BOS has yet to be evaluated. The strict application of standard lung donor criteria excludes a considerable number of lungs potentially suitable for transplantation, thus liberalisation of donor criteria might help to overcome donor shortage.     

Cow's Milk Exposure and Asthma in a Newborn Cohort: Repeated Ascertainment Indicates Reverse Causation

The effect of cow's milk consumption on childhood asthma has been debated for several years. This study attempts to provide further insight into this association through the use of a longitudinal study design. Newborns from parents with atopic history were recruited from Germany, Austria, and England (n = 696). For five repeated ascertainments, information was collected on cow's milk exposure, incidence of doctor-diagnosed asthma, and confounders. Generalized estimation equations, incorporating different models (concurrent, delayed, combined, and reverse causation), were used to determine this association. No association between cow's milk consumption and childhood asthma was found for the concurrent effects model (OR = 0.81, 95% confidence interval [CI]: 0.55, 1.20). In the delayed effects model, the direction of the association varied with time of follow-up. Thus, we stratified by period, which resulted in a significant protective delayed effect at 36 months (OR = 0.18, 95% CI = 0.06, 0.49). However, reverse causation negated this finding since the presence of asthma in prior months led to a reduction in further exposure to cow's milk (OR = 0.40, 95% CI = 0.16, 0.99). Hence, cow's milk consumption does not protect against childhood asthma. The apparent protection of cow's milk against asthma may result from parents of asthmatic children avoiding cow's milk, rather than actual prophylaxis.