The rapid increase of circulating adiponectin in neonatal calves depends on colostrum intake.

Adiponectin, an adipokine, regulates metabolism and insulin sensitivity. Considering that the transplacental transfer of maternal proteins of high molecular weight is hindered in ruminants, this study tested the hypothesis that the blood concentration of adiponectin in neonatal calves largely reflects their endogenous synthesis whereby the intake of colostrum might modify the circulating concentrations. We thus characterized the adiponectin concentrations in neonatal and young calves that were fed either colostrum or formula. Three trials were performed: in trial 1, 20 calves were all fed colostrum for 3 d, and then formula until weaning. Blood samples were collected on d 0 (before colostrum feeding), and on d 1, 3, 11, 22, 34, 43, 52, 70, 90, and 108 postnatum. In trial 2, 14 calves were studied for the first 4 d of life. They were fed colostrum (n=7) or formula (n=7), and blood samples were taken right after birth and before each morning feeding on d 2, 3, and 4. In trial 3, calves born preterm (n=7) or at term received colostrum only at 24 h postnatum. Blood was sampled at birth, and before and 2 h after feeding. Additionally, allantoic fluid and blood from 4 Holstein cows undergoing cesarean section were sampled. Adiponectin was quantified by ELISA. In trial 1, the serum adiponectin concentrations recorded on d 3 were 4.7-fold higher than before colostrum intake. The distribution of the molecular weight forms of adiponectin differed before and after colostrum consumption. In trial 2, the colostrum group had consistently greater plasma adiponectin concentrations than the formula group after the first meal. In trial 3, the preterm calves tended to have lower concentrations of plasma adiponectin than the term calves at birth and before and 2 h after feeding. Furthermore, the adiponectin concentrations were substantially lower in allantoic fluid than in the sera from neonatal calves and from cows at parturition. Our results show that calves are born with very low blood concentrations of adiponectin and placental transfer of adiponectin to the bovine fetus is unlikely. In conclusion, colostrum intake is essential for the postnatal increase of circulating adiponectin in newborn calves.

Associations of serum 25-hydroxycholecalciferol and parathyroid hormone with serum lipids differ by sex and vitamin D status.

OBJECTIVE: Although emerging evidence indicates an association between vitamin D and serum lipids, the data are still inconsistent. The purpose of the present study was to investigate whether 25-hydroxycholecalciferol (25-hydroxyvitamin D3; 25(OH)D3) or intact parathyroid hormone (iPTH) was independently related to serum lipids in elderly women and men. DESIGN: Cross-sectional study. Fasting serum levels of 25(OH)D3, iPTH, TAG, total cholesterol (TC), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) were assessed. Body composition was measured by bioelectrical impedance analysis. Lifestyle factors, such as nutrient intake, time spent outdoors, physical activity, smoking, supplement intake and medication, were assessed by questionnaires. Multiple regression analyses were performed to examine associations of 25(OH)D3 and iPTH with serum lipids. SETTING: Giessen, Germany. SUBJECTS: One hundred and ninety-three well-functioning German elderly aged 66-96 years. RESULTS: After adjusting for age, body fat, physical activity, smoking, alcohol intake, lipid-modifying drugs and either iPTH or 25(OH)D3, 25(OH)D3 was a predictor of TAG (standardised coefficient beta (ß)=-0.180), HDL-C (ß=0.197), LDL-C:HDL-C (ß=-0.298) and TC:HDL-C (ß=-0.302) in women, whereas iPTH was a predictor of HDL-C (ß=-0.297) in men. In sub-analysis, associations between 25(OH)D3 and TC (ß=-0.252), HDL-C (ß=0.230), LDL-C (ß=-0.324), LDL-C:HDL-C (ß=-0.412) and TC:HDL-C (ß=-0.380) were found in women with 25(OH)D3 concentrations above or equal the median vitamin D status (62.3 nmol/l), but not in women with lower 25(OH)D3 concentrations. CONCLUSIONS: In the elderly, associations of 25(OH)D3 and iPTH with serum lipids may differ by sex and may require a vitamin D status above 62 nmol/l.

Soluble α-klotho and its relation to kidney function and fibroblast growth factor-23.

CONTEXT: Relations between fibroblast growth factor-23 (FGF-23), soluble α-klotho (s-α-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α-klotho requires further study. OBJECTIVES: Our objectives were to analyze the relation of s-α-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-α-klotho to cholecalciferol. PATIENTS, DESIGN, AND SETTING: Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D and chronic renal insufficiency). INTERVENTIONS: Interventions included 40 000 IU cholecalciferol or placebo weekly. MAIN OUTCOME MEASURE: S-α-klotho was determined by ELISA with antihuman klotho antibodies 67G3 and 91F1. RESULTS: For all patients, s-α-klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations, a positive association of s-α-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-α-klotho below 204 pg/mL showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase compared with patients with higher s-α-klotho. Treatment with cholecalciferol significantly increased 1,25-dihydroxyvitamin D. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-α-klotho. CONCLUSIONS: CKD patients with s-α-klotho below 204 pg/mL had higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase. An association of s-α-klotho with eGFR was observed only in the presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-α-klotho concentrations.

S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population.

OBJECTIVE: Although homocysteine has been proposed as a cardiovascular risk factor, interventional trials lowering homocysteine have not consistently demonstrated clinical benefit. Recent evidence proposed the homocysteine metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by the kidneys, and cannot be lowered by vitamin supplementation. Due to its cumbersome measurement, data from large studies on the association between SAH, kidney function and cardiovascular disease are not available. METHODS: We recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among all study participants, we assessed parameters of C1 metabolism (homocysteine, SAH and S-adenosylmethionine), renal function (estimated glomerular filtration rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media-thickness [IMT]). eGFR was estimated by the CKD-EPIcreat-cys equation. RESULTS: Traditional cardiovascular risk factors and subclinical atherosclerosis were associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010; IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more closely correlated with SAH than with homocysteine (eGFR vs SAH: r = -0.335; p < 0.001; eGFR vs homocysteine: r = -0.250; p < 0.001). The association between eGFR and SAH remained significant after adjustment for traditional cardiovascular risk factors. CONCLUSION: In summary, cardiovascular risk factors, subclinical atherosclerosis and eGFR are more strongly associated with SAH than with homocysteine in apparently healthy subjects. Thus, SAH might represent a more promising target to prevent cardiovascular disease than homocysteine.

Lactation driven dynamics of adiponectin supply from different fat depots to circulation in cows.

Adipose tissue (AT) depots are heterogeneous in terms of morphology and adipocyte metabolism. Adiponectin, one of the most abundant adipokines, is known for its insulin sensitizing effects and its role in glucose and lipid metabolism. Little is known about the presence of adiponectin protein in visceral (vc) and subcutaneous (sc) AT depots. We assessed serum adiponectin and adiponectin protein concentrations and the molecular weight forms in vc (mesenterial, omental, and retroperitoneal) and sc (sternum, tail-head, and withers) AT of primiparous dairy cows during early lactation. Primiparous German Holstein cows (n = 25) were divided into a control (CON) and a conjugated linoleic acid (CLA) group. From day 1 of lactation until slaughter, CLA cows were fed 100 g of a CLA supplement/d (approximately 6% of cis-9, trans-11 and trans-10, cis-12 isomers each), whereas the CON cows received 100 g of a fatty acid mixture/d instead of CLA. Blood samples from all animals were collected from 3 wk before calving until slaughter on day 1 (n = 5, CON cows), 42 (n = 5 each of CON and CLA cows), and 105 (n = 5 each of CON and CLA cows) of lactation when samples from different AT depots were obtained. Adiponectin was measured in serum and tissue by ELISA. In all AT depots adiponectin concentrations were lowest on day 1 than on day 42 and day 105, and circulating adiponectin reached a nadir around parturition. Retroperitoneal AT had the lowest adiponectin concentrations; however, when taking total depot mass into consideration, the portion of circulating adiponectin was higher in vc than sc AT. Serum adiponectin was positively correlated with adiponectin protein concentrations but not with the mRNA abundance in all fat depots. The CLA supplementation did not affect adiponectin concentrations in AT depots. Furthermore, inverse associations between circulating adiponectin and measures of body condition (empty body weight, back fat thickness, and vc AT mass) were observed. In all AT depots at each time, adiponectin was present as high (approximately 300 kDa) and medium (approximately 150 kDa) molecular weight complexes similar to that of the blood serum. These data suggest differential contribution of AT depots to circulating adiponectin.

S0356: a phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma.

PURPOSE: Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival. PATIENTS AND METHODS: Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m(2) on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m(2)/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed for mRNA expression and polymorphisms in genes involved in drug metabolism and DNA repair. RESULTS: Ninety-three patients were evaluable. Two deaths (2.2%) were attributable to preoperative therapy, and two deaths (2.2%) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3% and 19.4% of patients, respectively. Seventy-nine patients (84.9%) underwent surgery; 67.7% of patients had R0 resections. Twenty-six patients (28.0%) had confirmed pCR (95% CI, 19.1% to 38.2%). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1%, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS. CONCLUSION: Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.

Effectiveness of various thermal ablation techniques for the treatment of nodular thyroid disease--comparison of laser-induced thermotherapy and bipolar radiofrequency ablation.

Alternative minimally invasive treatment options such as radiofrequency ablation (RFA) or laser-induced thermotherapy (LITT) are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. So far, studies have not been able to show a secure advantage for neither LITT nor RFA. The aim of this study was to compare the two ablation procedures in terms of their effectiveness. Thermal lesions were induced in porcine thyroid glands either by LITT or bipolar RFA ex vivo (n = 110 each) and in vivo (n = 10 each) using power settings between 10 and 20 W. Temperature spread during application was documented in 5- and 10-mm distance of the applicator. Postinterventional lesion diameters were measured and lesion size was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed in vivo. Lesion volumes induced by LITT ranged between 0.74 ± 0.18 cm(3) (10 W) and 3.80 ± 0.41 cm(3) (20 W) with a maximum of 5.13 ± 0.16 cm(3) at 18 W. The inducible lesion volumes by RFA were between 2.43 ± 0.68 cm(3) (10 W) and 0.91 ± 0.71 cm(3) (20 W) with a maximum of 2.80 ± 0.85 cm(3) at 14 W. The maximum temperatures were 112.9 ± 9.2°C (LITT) and 61.6 ± 13.9°C (RFA) at a distance of 5 mm and 73.2 ± 6.7°C (LITT) and 53.5 ± 8.6°C (RFA) at a distance of 10 mm. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage both for LITT and RFA. This study is the first to compare the effectiveness of laser-induced thermotherapy and radiofrequency ablation of thyroid tissue. LITT as well as RFA are suitable for singular thyroid nodules and induces reproducible clinically relevant lesions in an appropriate application time. The maximum inducible lesion volumes by LITT are significantly larger than by RFA with the devices used herein.

Sacral nerve stimulation induces changes in the pelvic floor and rectum that improve continence and quality of life.

PURPOSE: Sacral nerve stimulation (SNS) can improve fecal incontinence, though the exact mechanism is not known. This study examines the following hypotheses: SNS leads to contraction of the pelvic floor, influences rectal perception, and improves continence and quality of life. METHODS: Fourteen patients with sacral nerve stimulators implanted for fecal incontinence were examined prospectively. Morphological and functional assessment was done by endosonography, manometry, and volumetry with the stimulator turned on and off in direct succession. Questionnaires were used to determine incontinence and quality of life. RESULTS: With the stimulator turned on, rectal filling conditions were perceived only at higher volumes; in particular, the defecation urge was sensed only at higher volumes. There was also a reduction in the diameters of the external and internal anal sphincters and a decrease in the distance between the anal mucosa and the symphysis as a sign of pelvic floor elevation. Six months after surgery, continence and quality of life were markedly better than before the operation. CONCLUSIONS: We were able to confirm the hypotheses given above. The improvements of pelvic floor contraction and rectal perception are rapid adjustment processes in response to stimulation of sacral nerves S3/S4 when turning on the stimulator.

Ex vivo and in vivo evaluation of laser-induced thermotherapy for nodular thyroid disease.

BACKGROUND AND OBJECTIVE: The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like laser-induced thermotherapy (LITT) are increasingly used to treat tumors of parenchymatous organs and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for LITT of thyroid nodules. MATERIALS AND METHODS: Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n = 110) and in vivo (n = 10) using an Nd:YAG laser (1,064 nm). Laser energy was applied for 300 seconds in a power range of 10-20 W. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The lesions were longitudinally and transversally measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. RESULTS: The maximum inducible lesion volumes were between 0.74 +/- 0.18 cm(3) at a laser power of 10 W and 3.80 +/- 0.41 cm(3) at 20 W. The maximum temperatures after ablation were between 72.9 +/- 2.9 degrees C (10 W) and 112.9 +/- 9.2 degrees C (20 W) at a distance of 5 mm and between 49.5 +/- 2.2 degrees C (10 W) and 73.2 +/- 6.7 degrees C (20 W) at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. CONCLUSIONS: This study is the first to demonstrate a dose-response relationship for LITT of thyroid tissue. LITT is suitable for singular thyroid nodules and induces reproducible clinically relevant lesions with irreversible cell damage in an appropriate application time.

Analysis and occurrence of seven artificial sweeteners in German waste water and surface water and in soil aquifer treatment (SAT).

A method for the simultaneous determination of seven commonly used artificial sweeteners in water is presented. The analytes were extracted by solid phase extraction using Bakerbond SDB 1 cartridges at pH 3 and analyzed by liquid chromatography electrospray ionization tandem mass spectrometry in negative ionization mode. Ionization was enhanced by post-column addition of the alkaline modifier Tris(hydroxymethyl)amino methane. Except for aspartame and neohesperidin dihydrochalcone, recoveries were higher than 75% in potable water with comparable results for surface water. Matrix effects due to reduced extraction yields in undiluted waste water were negligible for aspartame and neotame but considerable for the other compounds. The widespread distribution of acesulfame, saccharin, cyclamate, and sucralose in the aquatic environment could be proven. Concentrations in two influents of German sewage treatment plants (STPs) were up to 190 microg/L for cyclamate, about 40 microg/L for acesulfame and saccharin, and less than 1 microg/L for sucralose. Removal in the STPs was limited for acesulfame and sucralose and >94% for saccharin and cyclamate. The persistence of some artificial sweeteners during soil aquifer treatment was demonstrated and confirmed their environmental relevance. The use of sucralose and acesulfame as tracers for anthropogenic contamination is conceivable. In German surface waters, acesulfame was the predominant artificial sweetener with concentrations exceeding 2 microg/L. Other sweeteners were detected up to several hundred nanograms per liter in the order saccharin approximately cyclamate > sucralose.

Laser-induced thermotherapy for lung tissue--evaluation of two different internally cooled application systems for clinical use.

Thermal ablation techniques like radiofrequency or laser-induced thermotherapy (LITT) are increasingly used to treat tumors of parenchymatous organs. Minimal access, parenchymal preservation, and a low complication rate render them suitable for pulmonary tumors as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for a percutaneous and an intraoperative system for LITT of lung tissue. Thermal lesions were induced in healthy porcine lungs using an Nd:YAG laser (1,064 nm). LITT was performed with a percutaneous application system in group I (n = 18) and an intraoperative application system in group II (n = 90). Laser energy was applied for 600-1,200 s in a power range of 20-32 W (12,000-38,400 J). The lesions were longitudinally and transversally measured, and the volume was calculated after the intervention. Furthermore, an open application system was used to perform LITT under in vivo conditions during lung perfusion and ventilation in domestic pigs. Lesion volumes in both groups showed a plateau-like curve when the laser power increased from an initial level of 25 W. With the percutaneous puncture system (group I), the application of 28 W (16,800 J) for 10 min generated the largest lesions with a volume of 12.54 +/- 1.33 cm(3), an axial diameter of 39.33 +/- 2.52 mm, and a diametrical diameter of 24.67 +/- 1.15 mm. A longer application time was not possible due to thermal instability of the applicator. Moreover, group I started developing extensive carbonizations at a laser power of 22 W (13,200 J). The intraoperative application system (group II) achieved the largest lesion volumes of 11.03 +/- 2.54 cm(3) with diameters of 34.6 +/- 4.22 mm (axial) and 25.6 +/- 2.51 mm (diametrical) by an exposure time of 20 min and a power of 32 W (38,400 J). Here extensive carbonizations only started to occur at 28 W (33,600 J). Under in vivo conditions, all pigs tolerated the LITT procedure well without complications. Besides a typical cooling effect in the vicinity of blood vessels, the thermal lesions were about three times smaller than the ex vivo lesions. Both the percutaneous and the open LITT application system induced reproducible, clinically relevant lung lesions. The percutaneous puncture set generated large relevant lesions, although its usability is limited by its restricted capacity and high carbonization risk. It is suitable for powers up to 22 W. The intraoperative application system allows higher energy exposure to induce larger lesion volumes. This study elucidates the dose-effect relation of two clinically relevant puncture sets.

Modeling interactions of Hg(II) and bauxitic soils.

The adsorptive interactions of Hg(II) with gibbsite-rich soils (hereafter SOIL-g) were modeled by 1-pK surface complexation theory using charge distribution multi-site ion competition model (CD MUSIC) incorporating basic Stern layer model (BSM) to account for electrostatic effects. The model calibrations were performed for the experimental data of synthetic gibbsite-Hg(II) adsorption. When [NaNO(3)] > or = 0.01M, the Hg(II) adsorption density values, of gibbsite, Gamma(Hg(II)), showed a negligible variation with ionic strength. However, Gamma(Hg(II)) values show a marked variation with the [Cl(-)]. When [Cl(-)] > or = 0.01M, the Gamma(Hg(II)) values showed a significant reduction with the pH. The Hg(II) adsorption behavior in NaNO(3) was modeled assuming homogeneous solid surface. The introduction of high affinity sites, i.e., >Al(s)OH at a low concentration (typically about 0.045 sites nm(-2)) is required to model Hg(II) adsorption in NaCl. According to IR spectroscopic data, the bauxitic soil (SOIL-g) is characterized by gibbsite and bayerite. These mineral phases were not treated discretely in modeling of Hg(II) and soil interactions. The CD MUSIC/BSM model combination can be used to model Hg(II) adsorption on bauxitic soil. The role of organic matter seems to play a role on Hg(II) binding when pH>8. The Hg(II) adsorption in the presence of excess Cl(-) ions required the selection of high affinity sites in modeling.

Vitamins are associated with survival in patients with end-stage renal disease: a 4-year prospective study.

BACKGROUND: Patients with end-stage renal disease are at high risk from premature death due mainly to cardiovascular disease and infections. Established risk factors do not sufficiently explain this increased mortality. We, therefore, investigated total mortality prospectively in a single-centre study in patients on hemodialysis and assessed the prognostic value of baseline disease status, laboratory variables including emerging risk factors, and the influence of vitamin treatment. METHODS: Patients (n = 102) were followed-up for 4 years or until death (n = 49). Survival was calculated by the Kaplan-Meier method. Cox-proportional hazards model was used to determine independent predictors of total mortality. RESULTS: The known risk factors age, baseline clinical atherosclerotic disease, low albumin and increased cardiac troponin T were significantly associated with mortality. Patients who received multivitamins during follow-up had a significantly lower mortality risk than those not receiving this treatment (hazard ratio 0.29, 95% confidence interval 0.15-0.56). These associations remained significant after adjustment for age, cardiovascular disease, albumin and cardiac troponin T at baseline. CONCLUSIONS: The present study suggests that multivitamin supplementation in patients with end-stage renal disease is closely associated with reduced mortality due to all causes. These observations have to be validated in randomized clinical intervention trials.

Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus aureus foreign body infection.

BACKGROUND: Daptomycin is a novel cyclic lipopeptide whose bactericidal activity is not affected by current antibiotic resistance mechanisms displayed by S. aureus clinical isolates. This study reports the therapeutic activity of high-dose daptomycin compared to standard regimens of oxacillin and vancomycin in a difficult-to-treat, rat tissue cage model of experimental therapy of chronic S. aureus foreign body infection. METHODS: The methicillin-susceptible S. aureus (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs, and time-kill curves of each antibiotic were evaluated as recommended by NCCLS, including supplementation with physiological levels (50 mg/L) of Ca2+ for daptomycin. Two weeks after local infection of subcutaneously implanted tissue cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin, oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple comparisons procedures. RESULTS: The MICs and MBCs of daptomycin, oxacillin, or vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L, respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of daptomycin compared to oxacillin or vancomycin. Twice-daily administered daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin) yielded bactericidal antibiotic levels in infected cage fluids throughout therapy. Before therapy, mean (+/- SEM) viable counts of strain I20 were 6.68 +/- 0.10 log10 CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (+/- SEM) reduction in viable counts of MSSA I20 was 2.62 (+/- 0.30) log10 CFU/mL in cages (n = 18) of daptomycin-treated rats, exceeding by > 2-fold (P < 0.01) the viable count reductions of 0.92 (+/- 0.23; n = 19) and 0.96 (+/- 0.24; n = 18) log10 CFU/mL in cages of oxacillin-treated and vancomycin-treated rats, respectively. Viable counts in cage fluids of untreated animals increased by 0.48 (+/- 0.24; n = 19) log10 CFU/mL. CONCLUSION: The improved efficacy of the twice-daily regimen of daptomycin (30 mg/kg) compared to oxacillin (200 mg/kg) or vancomycin (50 mg/kg) may result from optimisation of its pharmacokinetic and bactericidal properties in infected cage fluids.

Colorectal tumors and hepatic metastases differ in their optical properties-relevance for dosimetry in laser-induced interstitial thermotherapy.

BACKGROUND AND OBJECTIVES: The therapeutic application of laser light is a promising alternative to surgical resection of colorectal liver metastases. The extent of tumor destruction achieved by this strategy depends primarily on light distribution in the target tissue. Knowledge about optical properties is necessary to predict light distribution in the tissue for careful irradiation planning. The aim of this study was to compare the optical behavior of healthy colon tissue with that of colorectal carcinomas and their hepatic metastases in the native and coagulated state in order to test the effect of malignant degeneration, metastasis, and thermal coagulation on optical parameters. MATERIALS AND METHODS: Ninety tissue samples were taken from patients with a colorectal carcinoma and concomitant liver metastases: healthy colon tissue (n = 30); colon carcinoma (n = 30); liver metastases (n = 30). Optical properties were measured according to the single integrating sphere principle in the native state and after thermal coagulation in the wavelength range of 800-1,100 nm and analyzed by inverse Monte Carlo simulation. RESULTS: The highest optical penetration depth for all tissue types was obtained at the end of the spectral range investigated. The highest penetration depths of 4.13 mm (healthy colon), 7.47 mm (colon carcinoma tissue), and 4.08 (liver metastases) were at 1,060 nm, although the values decreased significantly after thermal coagulation. Comparing healthy colon-to-colon carcinoma always revealed a significantly lower absorption and scattering coefficient in the tumor tissue. This resulted in a higher optical penetration depth of the laser light in the colon carcinoma tissue (P < 0.05). A direct comparison disclosed no agreement between the optical properties of the primary tumor and the liver metastases. In the native state, colon carcinoma tissue had a lower scattering coefficient (P < 0.05), higher anisotropy factor, and optical penetration depth than liver metastases (P < 0.05). The absorption coefficient did not differ significantly. The differences in the native state were equalized by tissue coagulation. CONCLUSIONS: Colon carcinoma tissue has a higher optical penetration depth than healthy colon tissue, which speaks in favor of tumor selectivity for interstitial laser application, since large treatment volumes can be obtained in the tumor. The lack of agreement between primary tumors and their concomitant liver metastases indicates a modification of optical behavior through metastasis. Thermal coagulation of tissue leads to changes in the optical properties, which are clearly less pronounced in carcinoma tissue. The data obtained in this study clearly show that an individual irradiation schedule is necessary for effective and safe dosimetry in laser-induced thermotherapy (LITT).

In-vivo evaluation of a novel bipolar radiofrequency device for interstitial thermotherapy of liver tumors during normal and interrupted hepatic perfusion.

BACKGROUND: Only monopolar systems have thus far been available for radiofrequency ablation of liver tumors, whose application is restricted because of the incalculable energy flow, reduction of electrical tissue conduction, and limited lesion size. The aim of this study was to evaluate a novel internally cooled bipolar radiofrequency application device under in vivo conditions and to compare the effect of this system on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. MATERIALS AND METHODS: In a porcine liver model, RFA (60 W, 12 min) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle's maneuver, n = 12). RFA parameters (impedance, power output, temperature, applied energy) were determined continuously during therapy. RFA lesions were macroscopically assessed after liver dissection. RESULTS: Bipolar RFA induced clinical relevant ellipsoid thermal lesions without complications. Hepatic inflow occlusion led to a 4.3-fold increase in lesion volume after arterial microembolization and a 5.8-fold increase after complete interruption (7.4 cm(3)versus 31.9 cm(3)versus 42.6 cm(3), P < 0.01). CONCLUSIONS: The novel bipolar RFA device is a safe and effective alternative to monopolar RFA-systems. Interrupting hepatic perfusion significantly increases lesion volumes in bipolar RFA. This beneficial effect can also be achieved in the percutaneous application mode by RFA combined with arterial microembolization via a hepatic artery catheter.

Effectivity of laser-induced thermotherapy: in vivo comparison of arterial microembolization and complete hepatic inflow occlusion.

BACKGROUND AND OBJECTIVES: Laser-induced thermotherapy (LITT) is a promising method for local treatment of liver metastases. The aim of this study was to compare the effect of LITT on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. STUDY DESIGN/MATERIALS AND METHODS: In a porcine liver model, LITT (30 W 15 minutes) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle's maneuver, n = 12). LITT lesions were macro- and microscopically assessed after liver dissection. RESULTS: Hepatic inflow occlusion led to a fourfold increase in lesion volume after arterial microembolization and a ninefold increase after complete interruption (6.3. cm3 vs. 27.1 cm3 vs. 58.8 cm3, P < 0.01). CONCLUSIONS: Interrupting hepatic perfusion significantly increases lesion volumes in LITT. This beneficial effect can also be achieved in the percutaneous application mode by LITT combined with arterial microembolization via a hepatic artery catheter.

Enhancement of the immune response to residual intrahepatic tumor tissue by laser-induced thermotherapy (LITT) compared to hepatic resection.

BACKGROUND AND OBJECTIVES: In contrast to hepatic resection, thermally destroyed autologous tumor cells remain in situ after laser-induced thermotherapy (LITT). The aim of the study was to evaluate the effect of LITT and hepatic resection on the immune response to residual intrahepatic tumor tissue and the growth of untreated liver metastases. STUDY DESIGN/MATERIALS AND METHODS: Two independent adenocarcinomas (CC531) were implanted into 60 WAG rats, one in the right (control tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to further investigation 24 hours, 96 hours, 7 days, and 10 days after treatment. RESULTS: Ten days after treatment, control tumor volumes were 296+/-46 mm_ after LITT and 1,181+/-192 mm_, 1,387+/-200 mm_ after hepatic resection and no treatment, respectively (P<0.001). Peritoneal tumor spread was detected in 4/20 cases after LITT and in 17/20 cases after hepatic resection. Expression of CD8, B7-2 (CD86), and to lesser extent MHCII, LFA1 (CD11a), and ICAM1 (CD54), was significantly enhanced at the invasion front of control tumors after LITT compared to hepatic resection. CONCLUSIONS: Our results suggest that LITT increases the immune response against untreated intrahepatic tumor tissue, which can lead to reduced tumor growth.

Effects of reduced dialysate calcium on calcium-phosphorus product and bone metabolism in hemodialysis patients.

BACKGROUND: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. STUDY DESIGN: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D(3) (25-vit D(3)), 1,25-(OH)(2)-vitamin D(3) (1,25-vit D(3)), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. RESULTS: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol(2)/l(2) (at 18 months), whereas PTH increased from 81 +/- 57 pg/ml at baseline to 236 +/- 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D(3) and 1,25-vit D(3) subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 +/- 0.9 ng/ml, after 18 months: 1.1 +/- 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. CONCLUSION: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.