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.     

Elimination kinetics of maternally derived thyrotropin receptor-blocking antibodies in a newborn with significant thyrotropin elevation.

OBJECTIVE--To determine the course of maternally derived elevations in thyrotropin-binding inhibitory immunoglobulins in a neonate. DESIGN--Case report. SETTING--University pediatric endocrinology clinic and endocrine immunology laboratory in Ohio. PARTICIPANTS--An infant with elevated thyrotropin levels but near-normal total thyroxine levels, and her mother. INTERVENTIONS--None. MEASUREMENTS/MAIN RESULTS--Thyroid hormone, thyrotropin, and thyrotropin-blocking immunoglobulin concentrations were serially measured in a woman and her infant, who was found to have elevated thyrotropin levels (234 mU/L) and borderline low thyroxine levels (95 nmol/L). As infant thyroxine concentrations remained normal (125 to 145 nmol/L), no thyroxine supplementation was given. Thyrotropin levels decreased concomitantly with thyrotropin-blocking inhibitory immunoglobulin levels, and normalized by day 56 of life. The apparent elimination half-life of thyrotropin-blocking immunoglobulins was 7.5 days. CONCLUSIONS--The observed parallel elimination kinetics suggest that the thyrotropin receptor antibody acts as a thyrotropin antagonist, resulting in compensatory thyrotropin elevations. The duration of such elevations may be predicted on the basis of such elimination.     

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.     

Radiologische und histologische Beobachtungen an zentralen Talusfrakturen

In einer prospektiven Studie zentraler Talusfrakturen wurden radiologische Daten (Nativr?ntgenbild, CT, MRT) auf ihre Korrelation zum histologischen Befund (Biopsie zum Zeitpunkt der Schraubenentfernung) überprüft. Bei 9 Frakturen an 8 Patienten (Alter 14 – 48 Jahre) handelte es sich um Frakturen des Typs Hawkins I und II je einmal sowie des Typs III viermal; in 3 weiteren F?llen lagen K?rperfrakturen vor. Innerhalb von 24 h nach dem Unfall wurden 7 Frakturen verschraubt und 2 mit Bohrdr?hten adaptiert. Das verletzte Bein wurde für 14 – 53 Wochen post trauma vollst?ndig entlastet. Die Beobachtungszeit betrug mit einer Ausnahme 2 Jahre oder mehr; 4 Patienten zeigten am letzten R?ntgenbild einen intakten Talus, 4 Patienten zeigten partielle Einbrüche des Talusdoms und in 1 Fall war ein Teileinbruch fraglich. Die histologische Untersuchung (16 – 52 Wochen post trauma) zeigte in allen F?llen osteozytenfreien origin?ren Knochen mit Anlagerung neuen Knochens in individuell recht unterschiedlichem Ausma?. Das Hawkins-Zeichen war in 6 F?llen partiell positiv, sowie je einmal positiv und einmal negativ. Im CT konnte sowohl Dekalzifikation als auch Frakturheilung besser als im R?ntgenbild beobachtet werden. Das MRT-Signal war 5mal normal, 2mal partiell und einmal komplett pathologisch. Positives Hawkins-Zeichen und normales Signalverhalten sind prognostisch günstig zu werten. Es kam jedoch in Folge zentraler Talusfraktur auch bei radiologisch günstigem Verlauf zur Osteonekrose wenigstens von Teilen Talus gefolgt von schleichendem Ersatz. Die offenbar bei jeder zentralen Talusfraktur gest?rte Vaskularisation wurde von keinem radiologischen Befund einwandfrei reflektiert.