Cardiac Risks in Multimodal Breast Cancer Treatment

Strahlentherapie und Onkologie -     

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.     

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.      

Changes in ventilatory mechanics and diaphragmatic function after lung volume reduction surgery in patients with COPD

BACKGROUND: Lung volume reduction (LVR) has recently been used to treat severe emphysema. About 25% of the volume of each lung is removed with this method. Little is known about the mechanism of functional improvement so a study was undertaken to investigate the changes in ventilatory mechanics and diaphragmatic function in eight patients after LVR. METHODS: Measurements of work of breathing (WOB), intrinsic positive end expiratory pressure (PEEPi), dynamic compliance (Cdyn), and arterial carbon dioxide tension (PaCO2) were performed on the day before surgery and daily for seven days after surgery, as well as one, three, and six months after surgery. All measurements were performed on spontaneously breathing patients, simultaneously assessing oesophageal pressure via an oesophageal balloon catheter and air flow via a tightly adjusted mask. Diaphragmatic function was evaluated by measuring oesophageal and transdiaphragmatic pressure (Pdi) preoperatively and at one, three, and six months postoperatively. RESULTS: Mean forced expiratory volume in one second (FEV1) was 23 (3.6)% predicted, and all patients were oxygen dependent before the-operation. One day after LVR the mean decrease in WOB was 0.93 (95% confidence interval (CI) 0.46 to 1.40) joule/l, the mean decrease in PEEPi was 0.61 (95% CI 0.35 to 0.87) kPa, and the mean increase in Cdyn was 182.5 (95% CI 80.0 to 284.2) ml/kPa. Similar changes were found seven days and six months after surgery. PaCO2 was higher on the day after the operation but was significantly reduced six months later. Pdi was increased three and six months after surgery. CONCLUSIONS: Ventilatory mechanics improved immediately after LVR, probably by decompression of lung tissue and relief of thoracic distension. An improvement in diaphragmatic function three and six months postoperatively also contributes to improved respiratory function after LVR.