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Hypohydration exceeding 2% body mass can impair endurance capacity. It is postulated that the brain could be perturbed by hypohydration, leading to impaired motor performance. We investigated the neural effects of hypohydration with magnetic resonance imaging (MRI). Ten men were dehydrated to approximately −3% body mass by running on a treadmill at 65% maximal oxygen consumption (V̇o2max) before drinking to replace either 100% [euhydration (EU)] or 0% [hypohydration (HH)] of fluid losses. MRI was performed before start of trial (baseline) and after rehydration phase (post) to evaluate brain structure, cerebral perfusion, and functional activity. Endurance capacity assessed with a time-to-exhaustion run at 75% V̇o2maxwas reduced with hypohydration (EU: 45.2 ± 9.3 min, HH: 38.4 ± 10.7 min; P = 0.033). Mean heart rates were comparable between trials (EU: 162 ± 5 beats/min, HH: 162 ± 4 beats/min; P = 0.605), but the rate of rise in rectal temperature was higher in HH trials (EU: 0.06 ± 0.01°C/min, HH: 0.07 ± 0.02°C/min; P < 0.01). In HH trials, a reduction in total brain volume (EU: +0.7 ± 0.6%, HH: −0.7 ± 0.9%) with expansion of ventricles (EU: −2.7 ± 1.6%, HH: +3.7 ± 3.3%) was observed, and vice versa in EU trials. Global and regional cerebral perfusion remained unchanged between conditions. Functional activation in the primary motor cortex in left hemisphere during a plantar-flexion task was similar between conditions (EU: +0.10 ± 1.30%, HH: −0.11 ± 0.31%; P = 0.637). Our findings demonstrate that with exertional hypohydration, brain volumes were altered but the motor-related functional activity was unperturbed.NEW & NOTEWORTHY Dehydration occurs rapidly during prolonged or intensive physical activity, leading to hypohydration if fluid replenishment is insufficient to replace sweat losses. Altered hydration status poses an osmotic challenge for the brain, leading to transient fluctuations in brain tissue and ventricle volumes. Therefore, the amount of fluid ingestion during exercise plays a critical role in preserving the integrity of brain architecture. These structural changes, however, did not translate directly to motor functional deficits in a simple motor task.

OBJECTIVE: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury.METHODS: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury.RESULTS: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage.INTERPRETATION: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies. Ann Neurol 2016;79:970-982. (Less)

The measurement of skinfold thickness by means of skinfold callipers (SC) is a widely accepted method to assess subcutaneous fat thickness and percentage body fat (%BF). Ultrasound imaging (USI) is a more recent technology that is becoming accessible for the same application. The objective of this study was to compare measurements recorded by SC and USI for the assessment of subcutaneous fat thickness in order to estimate %BF. Thirty adults volunteered for the study. Body mass, stature and subcutaneous fat thickness for seven sites were measured. Strong (p0.05) difference between the %BF determined by the two methods (SC=19.5±6.4 %BF and USI = 19.0±6.3 %BF). However, levels of agreement indicated that the USI could over- or underestimate %BF by ±10%. This resulted in %BF estimation errors which are deemed too large from a clinical perspective. Additional studies are recommended to investigate the lack of agreement and bias highlighted between the two methods.Keywords: Percentage body fat, field assessments, subcutaneous fat thickness

OBJECTIVES The purpose of this study was use molecular imaging targeting coagulation pathway and inflammation to better understand the pathophysiology of silent brain ischemia (SBI) and monitor the effects of factor XIIa inhibition. BACKGROUND SBI can be observed in patients who undergo invasive vascular procedures. Unlike acute stroke, the diffuse nature of SBI and its less tangible clinical symptoms make this disease difficult to diagnose and treat. METHODS We induced SBI in mice by intra-arterial injection of fluorescently labeled microbeads or fractionated clot into the carotid artery. After SBI induction, diffusion-weighted magnetic resonance imaging was performed to confirm the presence of microinfarcts in asymptomatic mice. Molecular imaging targeting the downstream factor XIII activity (single-photon emission computed tomography/ computed tomography) at 3 h and myeloperoxidase activity (magnetic resonance imaging) on day 3 after SBI induction were performed, without and with the intravenous administration of a recombinant selective factor XIIa inhibitor derived from the hematophagous insect Triatoma infestans (rHA-Infestin-4). Statistical comparisons between 2 groups were evaluated by the Student t test or Mann-Whitney U test. RESULTS In SBI-induced mice, we found abnormal activation of the coagulation cascade (factor XIII activity) and increased inflammation (myeloperoxidase activity) close to where emboli lodge in the brain. rHA-Infestin-4 administration significantly reduced ischemic damage (53% to 85% reduction of infarct volume, p 0.05) and pathological coagulation (35% to 39% reduction of factor XIII activity, p 0.05) without increasing hemorrhagic frequency. Myeloperoxidase activity, when normalized to the infarct volume, did not significantly change with rHA-Infestin-4 treatment, suggesting that this treatment does not further decrease inflammation other than that resulting from the reduction in infarct volume. CONCLUSIONS Focal intracerebral clotting and inflammatory activity are part of the pathophysiology underlying SBI. Inhibiting factor XIIa with rHA-Infestin-4 may present a safe and effective treatment to decrease the morbidity of SBI. (J Am Coll Cardiol Img 2012;5:1127–38) © 2012 by the American College of Cardiology Foundation

Although distraction osteogenesis (DO) is widely used, there is minimal information on its use in patients after radiotherapy. The mutilating effects of ablative head and neck surgery, and insufficient development of the craniofacial skeleton after childhood head and neck malignancies, frequently necessitate complex reconstruction techniques. The simultaneous expansion of soft tissue that comes with bony lengthening during DO is a unique phenomenon.1 In selected cases, it causes less morbidity and better esthetic results than any other surgical procedure. The effects of radiotherapy on the outcome of DO are still not clear. There are only a few case reports describing DO of the human craniofacial skeleton after radiotherapy. Most of these reports have dealt with mandibular DO.2, 3 and 4 Only 1 case of postradiotherapy midface DO has been described thus far. Grover et al5 presented a patient with radiation-induced orbital zygomatic hypoplasia, which was treated using a rigid external distraction device. Several animal studies have been performed to explore the advantages of hyperbaric oxygen in postradiation DO, but these studies were confined to mandibles.6 and 7 In the present article, 2 patients are presented with radiation-induced midfacial hypoplasia after childhood malignancies. These patients were successfully treated with rigid external DO in combination with hyperbaric oxygen (HBO) therapy.

The extent to which humans need to replace fluid losses during exercise remains contentious despite years of focused research. The primary objective was to evaluate ad libitum drinking on hydration status to determine whether body mass loss can be used as an accurate surrogate for changes in total body water (TBW) during exercise. Data were collected during a 14.6-km route march (wet bulb globe temperature of 14.1°C ). 18 subjects with an average age of 26 ± 2.5 (SD) years participated. Their mean ad libitum total fluid intake was 2.1 ± 1.4 litres during the exercise. Predicted sweat rate was 1.289 ± 0.530 l/h. There were no significant changes (p>0.05) in TBW, urine specific gravity or urine osmolality despite an average body mass loss (p

SummaryCrohn’s disease (CD) is associated with reduced bone mineral density and increased fracture risk. To assess the effects of the inflammatory process itself on bone parameters, we investigated patients with active CD and in remission without glucocorticoid treatment four weeks prior to analysis. Patients with active CD were compared to age-and sex-matched healthy volunteers and osteoporosis patients. Bone mineral density, bone formation and resorption markers were assessed, in addition to simple inflammatory markers and cytokines. Out of seven patients with active disease, three had osteopenia and one osteoporosis (WHO definition). The erythrocyte sedimentation rate (ESR) was associated with BMD at the femoral neck (R2 = 0.853, p < 0.01) and the spine (R2 = 0.772, p < 0.05). ESR seems to influence bone formation, as shown by lower bone alkaline phosphatase with high ESR (R2 = 0.725, R = – 0.852, p < 0.05). The clinical disease activity score was not useful in determining patients’ risk of acquiring bone disease. In conclusion, in patients with Crohn’s disease, the degree of the inflammatory process as assessed by ESR indicates bone loss and might be of value in identifying patients at risk of developing osteoporosis.

Background Diabetes in liver cirrhosis is associated with a blunted insulin response, which might be explained by an impaired release of the incretin hormone glucagon-like peptide 1 (GLP-1) into the portal circulation. Aims To investigate basal and stimulated portal venous and peripheral GLP-1 concentrations in non-diabetic (ND) and diabetic (D) patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic stent shunt (TIPSS) implantation. Patients and methods After elective TIPSS portalvenous and peripheral probes were drawn from 10 ND and 10 D patients with stable liver disease during an oral metabolic test and plasma glucose, immunoreactive GLP-1, insulin and C-peptide were measured. Results The study meal led to a significant rise in portal GLP-1 levels in ND and D. Basal and stimulated portal GLP-1 concentrations were not significantly different between ND and D. Peripheral GLP-1 did not differ significantly from portal venous levels. Insulin response in ND was more pronounced in the portal blood than in the periphery and was absent in D. Conclusion TIPSS allows a direct evaluation of hormonal changes in the portal circulation during an oral metabolic tolerance test. A disturbed GLP-1 secretion does not play a role in blunting the insulin response observed in patients with hepatogenous diabetes.

A now 20-year-old man has been suffering from diabetes insipidus for four years. Two years ago a tumour in the hypophyseal stalk-hypothalamus region had been removed, but no definitive histological diagnosis could be established. When aged 19 he developed cutaneous changes which for the first time led to histiocytosis being suspected. Also for the first time, multiple small foci were noted in both lungs. Histological examination of a transbronchial lung biopsy demonstrated histiocytosis X. No specific treatment is being considered at present, because the patient is symptom-free and has normal lung function.

History and clinical findings A 41-year-old woman, known for 10 month to have polycythaemia vera, developed severe right upper abdominal pain. The abdomen was tense from marked ascites and the liver enlarged by 18 cm in the mid-clavicular line. Investigations Serum bilirubin was slightly elevated to 2.2mg/dl, liver synthesis being much reduced (recalcifying time minimally 23%, albumin minimally 2.8 g/dl). Doppler sonography detected no flow in the right and middle hepatic veins, indicating Budd-Chiari syndrome. Portal vein flow was diminished. Treatment and course Heparin treatment had to be stopped because of heparin-associated type II thrombocytopenia and hirudin was substituted. Attempted lysis with a total of 100 mg r-tPA failed. As the patient's condition deteriorated a TIPSS was implanted to provide portal decompression. Incomplete portal vein thrombosis was demonstrated and worsened during the procedure until nearly complete occlusion. Local lysis treatment for 2 days with urokinase, 50,000-60,000 U/h, and two shunt revisions finally succeeded in completely dissolving the thrombus. Portocaval pressure fell from 32 to 21 mm Hg, and the size and function of the liver became almost normal and the ascites disappeared. Anticoagulation with a coumarin derivative was started and hydrocarbamide again given for recurrent thrombocytosis. The patient remained largely symptom-free one year after TIPSS. Conclusion This case demonstrates the effectiveness of TIPSS in Budd-Chiari syndrome, even in complicated portal vein thrombosis.

HISTORY AND CLINICAL FINDINGS: A 55-year-old woman with known primary biliary cirrhosis (PBC) was hospitalized because of increasing dyspnoea. A year before she had for the first time experienced a right-sided pleural effusion which had to be drained every 4 weeks. Physical examination revealed dullness on percussion and greatly decreased breath sounds on auscultation over the entire right thorax. In addition there were signs of moderate ascites and leg oedema. INVESTIGATIONS: Chest radiograph showed a homogeneous shadowing of the right thorax without mediastinal shift. Diagnostic thoracocentesis produced a serous effusion, a transudate on chemical analysis, comparable to the composition of the ascitic fluid. Bacteriological and cytological tests on both fluids were unremarkable. TREATMENT AND COURSE: The right pleural effusion was presumed to be due to a hydrothorax from the ascites caused by portal hypertension associated with the PBC. Despite continuous diuretic treatment and thoracocentesis with albumin substitution every 3 days there was no improvement and implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) was performed. This effectively lowered portal pressure and markedly improved the patient's condition so that further thoracocentesis were no longer necessary. 3 weeks after TIPSS implantation she was discharged in good condition. Radiography 3 weeks later demonstrated continued reduction in the hydrothorax. CONCLUSION: Hydrothorax is a rare complication of liver cirrhosis. TIPSS implantation can provide lasting resolution and corresponding clinical improvement of a hydrothorax, especially in those conditions which are refractory to diuretic treatment and thoracocentesis.

Haemostasis including blood coagulation is initiated upon vessel wall injury and indispensable to limit excessive blood loss. However, unregulated pathological coagulation may lead to vessel occlusion, causing thrombotic disorders, most notably myocardial infarction and stroke. Furthermore, blood exposure to foreign surfaces activates the intrinsic pathway of coagulation. Hence, various clinical scenarios, such as extracorporeal membrane oxygenation, require robust anticoagulation consequently leading to an increased bleeding risk. This study aimed to further assess the antithrombotic efficacy of the activated factor XII (FXIIa) inhibitor, rHA-Infestin-4, in several thrombosis models. In mice, rHA-Infestin-4 decreased occlusion rates in the mechanically-induced arterial (Folt's) and the FeCl3 -induced venous thrombosis model. rHA-Infestin-4 also protected from FeCl3 -induced arterial thrombosis and from stasis-prompted venous thrombosis in rabbits. Furthermore, rHA-Infestin-4 prevented occlusion in the arterio-venous shunt model in mice and rabbits where thrombosis was induced via a foreign surface. In contrast to heparin, the haemostatic capacity in rabbits was unaffected by rHA-Infestin-4. Using rodent and non-rodent species, our data demonstrate that the FXIIa inhibitor rHA-Infestin-4 decreased arterial, venous and foreign surface-induced thrombosis without affecting physiological haemostasis. Hence, we provide further evidence that targeting FXIIa represents a potent yet safe antithrombotic treatment approach, especially in foreign surface-triggered thrombosis.

Virtual clinical trials (VCT) can be carefully designed to inform, orient, or potentially replace clinical trials. The focus of this study was to demonstrate the capability of the sophisticated tools that can be used in the design, implementation, and performance analysis of VCTs, through characterization of the effect of background tissue density and heterogeneity on the detection of irregular masses in digital breast tomosynthesis. Twenty breast phantoms from the extended cardiactorso (XCAT) family, generated based on dedicated breast computed tomography of human subjects, were used to extract a total of 2173 volumes of interest (VOI) from simulated tomosynthesis images. Five different lesions, modeled after human subject tomosynthesis images, were embedded in the breasts, for a total of 6×2173 VOIs with and without lesions. Effects of background tissue density and heterogeneity on the detection of the lesions were studied by implementing a doubly composite hypothesis signal detection theory paradigm with location known exactly, lesion known exactly, and background known statistically. The results indicated that the detection performance as measured by the area under the receiver operating characteristic curve (ROC) deteriorated as density was increased, yielding findings consistent with clinical studies. The detection performance varied substantially across the twenty breasts. Furthermore, the log-likelihood ratio under H0 and H1 seemed to be affected by background tissue density and heterogeneity differently. Considering background tissue variability can change the outcomes of a VCT and is hence of crucial importance. The XCAT breast phantoms can address this concern by offering realistic modeling of background tissue variability based on a wide range of human subjects.

We examined a 41-year-old female with a subacute Budd-Chiari Syndrome (BCS) before and after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) by means of digital electroencephalography (EEG). After TIPSS implantation hepatic decompression had been achieved and the liver function as well as the clinical status improved daily. Simultaneously, the digital EEG showed a decrease in the power of the theta band and an increase in the physiological alpha frequency band. The theta/alpha ratio decreased after TIPSS, despite an elevated arterial ammonia level. The patient had a well-preserved liver parenchyma before the occurrence of the BCS. After portal decompression by TIPSS, the liver function normalized and the liver resumed efficient synthesis and parts of its detoxification task. This regeneration capacity was documented by a rise in cholinesterase after TIPSS. After temporary substitution of albumin the serum albumin concentration returned to normal. Thus, some neurotoxic substances with high albumin-binding capacity may not be absorbed by the central nervous system (CNS). Furthermore, it appears likely that the length of time the brain is exposed to neurotoxic substances plays a role in the clinical and electroencephalographic changes. Compared to the conventional EEG the theta/alpha ratio reflected better metabolically conditioned electroencephalographic changes after TIPSS.

Rectal stricture is a serious although infrequent complication of transanal endoscopic microsurgery (TEM). In some cases, these strictures may be refractory to treatment by endoscopic balloon dilatation. Biodegradable stents might improve the outcome by providing an extended period of dilatation. Moreover, these stents can remain in place without the need to remove them. In the presented case, a biodegradable polidioxanone stent originally developed to treat benign oesophageal stenoses was used to treat a patient suffering from rectal stricture following a TEM.

Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74% ethyltoxic men, 50% ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls. In women ascitic-free BMI significantly increased (from 22.8 +/- 4.6 kg/m2 to 23.9 +/- 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 +/- 4.7 vs. 26.7 +/- 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 +/- 8.8 ng/ml vs. 18.6 +/- 14.9; p = 0.009) and in men (7.7 +/- 6.2 ng/ml vs. 12.2 +/- 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 +/- 0.29 vs. 0.73 +/- 0.52; p = 0.017; men 0.28 +/- 0.22 vs. 0.43 +/- 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations. After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.

A patient with suspected liver metastases detected by routine sonography of the abdomen was admitted to our clinic for further testing. Liver sonography disclosed multiple irregular gyriform foci of a hyperechoic structure with a maximum diameter of 3.5 cm. In magnetic resonance imaging, these foci appeared as hyperintense in T1-weighted images and isointense in T2-weighted images. A biopsy showed a discrete portal and periportal fibrosis. UV light fluorescence of the specimen was negative. Analysis of urine revealed an almost fourfold el-evation of total porphyrin of 591 µg/24 h, proving the diagnosis of chronic hepatic porphyria. Characteristic liver foci in hepatic porphyria are detected by sonography in some affected patients. Usually, they can also be depicted by magnetic resonance imaging and computed tomography. These foci often appear before any other symptoms of the disease and are reversible when triggering factors, such as certain drugs or alcohol, are discontinued.

Aim Therapeutic options for primary and secondary liver tumours not suitable for resection or transplantation are limited. In this palliative situation, the scope of ablative therapeutic procedures has improved. Laser interstitial thermotherapy is a minimal invasive procedure for local tumour destruction within solid organs. This pilot study reports initial clinical experience using ultrasound-guided percutaneous laser interstitial thermotherapy. Methods Sixty patients between the ages of 34 and 78 years with non-resectable primary and secondary liver tumours were treated palliatively with Nd:YAG laser interstitial thermotherapy. High resolution abdominal ultrasound with power duplex was used to control the placement and coagulation procedure. Results In all cases, sonographic imaging allowed exact placement of the laser probe and verification of thermocoagulation by a resulting hyperechogenic signal enhancement. The maximum diameter of laser-induced destruction measured 5 cm. Ultrasound with power duplex and echo enhancer, CT or MRI scans indicated necrosis of treated tumour lesions. No serious adverse event occurred and 30-day-mortality was zero. Conclusions Ultrasound-guided laser interstitial thermotherapy is safe and reliably ablates primary and secondary liver tumours. The combination of high resolution ultrasound and laser therapy facilitates a minimally invasive but elaborate treatment. Besides chemotherapy, this procedure could be a useful palliative treatment to control the mass of liver tumours unsuitable for resection or transplantation.

In dem hier vorgestellten Fall handelt es sich um einen jungen Mann, der bereits seit mehreren Monaten kontinuierlich an Gewicht abgenommen hatte. Ursache war eine Schluckstorung auf dem Boden einer sowohl endoskopisch als auch histopathologisch ausgepragten eosinophilen Osophagitis. Wie in der Literatur beschrieben kam es auch bei unserem Patienten durch den Einsatz topischer Kortikoide kurzfristig zu einer deutlichen Verbesserung sowohl der objektiven Befunde als auch der Beschwerden. Anhand eines Literaturuberblickes wird auf atiopathogenetische und klinische Aspekte dieses Krankheitsbildes eingegangen.

Summary objective We observed the new onset of severe obstructive sleep apnoea syndrome (OSAS) in an adult male patient during human growth hormone (hGH) replacement therapy. This prompted us to evaluate the potential influence of hGH substitution therapy on sleep in middle-aged men. design A longitudinal study. subjects Five male patients (aged 44–56 years, median age 54 years) with postoperative pituitary insufficiency given hGH replacement therapy for 1–2 years (median dose 2·0 U/day; median IGF-I serum concentration 351 µg/l) and 6 months after cessation of hGH treatment (median IGF-I level 77 µg/l – 1 µg/l = 0·131 nmol/l). measurements Polysomnographic studies were performed, and the following parameters were determined: time in bed (TIB), sleep period time (SPT), total sleep time (TST), sleep efficiency (SE = TST/TIB), sleep stage 1 onset latency (SL), different sleep stages [W (wake), S1, S2, SWS (slow wave sleep = S3 + S4) and REM; % of SPT], stage shifts per hour of SPT (SS/h), stage shifts to W/h of SPT [A/h (awakening)], index of apnoea and hypopnoea events per hour of TST (AH/h), arousals from apnoea and hypopnoea per hour of TST (Ar/h), index of obstructive (OAH/h), central (CAH/h) and mixed (MAH/h) events of apnoea and hypopnoea per hour of TST and minimal desaturation (MD). results Median baseline results were: TIB, 479 min; SPT, 465 min; TST, 405 min; SE, 77%; SL, 8·5 min; W, 18·9%; S1, 8·2%; S2, 52·7%; REM, 13·5%; SS/h, 17·7; A/h, 2·8; AH/h, 11·9; Ar/h, 4·4; MD, 80%. These parameters did not change significantly after cessation of hGH treatment. In contrast, median SWS decreased significantly from 33 min (7·1%) to 7·5 min (1·8%; P = 0·03). Median OAH/h decreased significantly from 4·4 to 0·1 (P = 0·03) whereas CAH/h increased from 6·3 to 14·6 (P = 0·03) after cessation of hGH. Correspondingly, one patient with OSAS improved markedly whereas another patient developed new and asymptomatic central SAS after cessation of hGH. conclusion This study showed that hGH replacement therapy influenced sleep reaction in a complex way in middle-aged men; cessation of treatment was associated with a significant decrease in slow wave sleep and a shift from obstructive to central apnoea and hypopnoea.

The aim of the study was the quantification of metabolically caused electroencephalographic changes of portal-systemic encephalopathy, a prototype of hepatic encephalopathy. We examined 12 patients with liver cirrhosis before and after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) by means of quantitative digital electroencephalography (EEG). One month after TIPSS implantation, all patients showed an increase in the power of the theta frequency band as well as a decrease in the power of the alpha frequency band. To reduce the error variance, we formed the quotient of the relative power of the theta and alpha frequency band. Theta/alpha quotient values over 0.7 indicate a general change of the EEG with a sensitivity of 93% and a specificity of 87%. The results we have to hand indicate a correlation between the albumin concentration and the theta/alpha quotient 1 and 3 months after TIPSS. No significant correlation was revealed with regard to the Child-Pugh score or the liver function parameters cholinesterase, bilirubin, and prothrombin time. Neither the arterial ammonia concentration nor the performance in the psychometric test showed significance in relation to the theta/alpha quotient. Substances with a high albumin bond and potential neurotoxicity may—in the case of lower albumin levels—be absorbed with increased frequency in the CNS and may be responsible for the observed EEG change.

Mammography is currently the most widely utilized tool for detection and diagnosis of breast cancer. However, in women with dense breast tissue, tissue overlap may obscure lesions. Digital breast tomosynthesis can reduce tissue overlap. Furthermore, imaging with contrast enhancement can provide additional functional information about lesions, such as morphology and kinetics, which in turn may improve lesion identification and characterization. The performance of these imaging techniques is strongly dependent on the structural composition of the breast, which varies significantly among patients. Therefore, imaging system and imaging technique optimization should take patient variability into consideration. Furthermore, optimization of imaging techniques that employ contrast agents should include the temporally varying breast composition with respect to the contrast agent uptake kinetics. To these ends, we have developed a suite of 4-D virtual breast phantoms, which are incorporated with the kinetics of contrast agent propagation in different tissues and can realistically model normal breast parenchyma as well as benign and malignant lesions. This development presents a new approach in performing simulation studies using truly anthropomorphic models. To demonstrate the utility of the proposed 4-D phantoms, we present a simplified example study to compare the performance of 14 imaging paradigms qualitatively and quantitatively.

Traumatic brain injury (TBI) induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 hour. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 hour after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted antiinflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings.

Background/Aims : Liver cirrhosis is frequently associated with sexual dysfunction and hormonal abnormalities. To evaluate the effect of portosystemic shunting on sex steroid serum concentrations, a prospective study was performed in cirrhotic patients treated consecutively and electively by transjugular intrahepatic portosystemic stent shunt (TIPS). Methods : In 27 patients with liver cirrhosis we measured serum levels of testosterone (T), sexual hormone binding globulin (SHBG), luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, androstenedione (A), estradiol (E 2 ), 17-OH-progesterone and the T/SHBG ratio before and 3 months after TIPS. Results : In men (n=17) 3 months after TIPS, A and E 2 significantly increased, with mean serum levels rising from 4.4±2.5 to 5.6±2.9 ng/ml (P=0.04) and from 27±9 to 40±19 pg/ml (P=0.003), respectively. In contrast to A the increase of E 2 persisted at 9 and 15 months after TIPS. Erectile dysfunction increased from 30% before TIPS to 70% after TIPS. In women (n=10) A and E 2 levels did not change significantly after TIPS. Conclusions : TIPS aggravated hormonal dysbalance of sex steroids in favor of estrogens (hyperestrogenism) in men.

Hintergrund: Das kolorektale Karzinom stellt trotz einer Abnahme von Inzidenz und Todesrate die zweithaufigste tumorbedingte Todesursache in der westlichen Welt dar. Ungeachtet der Erfolge operativer Verfahren (Stichwort Tumorchirurgie) und der adjuvanten Therapie entwickeln sich insbesondere bei lokal fortgeschrittenen Primartumoren haufig Rezidive und Metastasen, die eine kurative Behandlung nicht mehr erlauben. In dieser palliativen Situation, die haufig auch schon bei der initialen Prasentation besteht, ist neben einer bestmoglichen supportiven Therapie eine differenzierte und abgestufte Chemotherapie angeraten. Eine palliative Chemotherapie verzogert die Krankheitsprogression und verbessert Lebensqualitat und Uberleben (von 6–9 Monaten auf 15–18 Monate). Mit einer Chemotherapie sollte bereits im asymptomatischen Stadium bei nachweisbarem Krankheitsprogress begonnen werden. Chemotherapie: Eckpfeiler der palliativen Chemotherapie ist weiterhin das 5-Fluorouracil (5-FU). Die Wirkungen und die Nebenwirkungen sind entscheidend abhangig von der Darreichungsform und der Biomodulation (z. B. durch Calciumfolinat in Form von Leucovorin [LV]). Hervorzuheben ist besonders die 24-stundige Infusionsbehandlung mit 5-FU/LV, die wir gegenuber der traditionellen Bolustherapie aus Grunden der hoheren Effektivitat bei weniger Nebenwirkungen in der Primartherapie des kolorektalen Karzinoms bevorzugen. Weitere Substanzen, die additiv bzw. alternativ zum 5-FU eingesetzt werden konnen, umfassen Natriumfolinat, Raltitrexed, und orale Fluoropyrimidinanaloga (sog. Prodrugs) wie Capecitabine und Tegafur-Uracil (UFT). Diese Pharmaka sind z. Z. noch in der klinischen Erprobung. Insbesondere das Capecitabine erscheint als sinnvolle Alternative zur intravenosen 5-FU-Therapie. Capecitabine ist dem traditionellen 5-FU-Bolusschema (Mayo-Schema) bei weniger Nebenwirkungen mindestens ebenburtig. Es hat zudem den Vorteil, dass es oral gegeben werden kann. Bei Versagen einer 5-FU-Behandlung kommen in der Zweit- und Drittlinientherapie Oxaliplatin bzw. Irinotecan mit einer Ansprechrate (i. S. einer partiellen Remission) von 10 bzw. 13–15% zum Einsatz. Erstlinientherapie: Vier randomisiserte Phase-III-Studien des Jahres 2000 belegen den Nutzen einer additiven Gabe von Oxaliplatin und Irinotecan zuzuglich zu 5-FU/LV auch in der Primartherapie des kolorektalen Karzinoms. Sie zeigen ubereinstimmend eine hohere Ansprechrate und eine verbesserte Lebensqualitat unter der Tripeltherapie und unter Therapie mit Irinotecan/5-FU/LV sogar eine verbesserte Uberlebensrate. Diesem Erfolg stehen eine hohere Nebenwirkungsrate und ein hoherer Therapiepreis gegenuber.

OBJECTIVE: Both multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are caused by germline mutations of the RET proto-oncogene. A broad spectrum of malignancy within and between families has been described with no clear genotype-phenotype correlation due to a scarcity of available data of large kindreds. DESIGN: Here we present the only known family with a germline mutation of codon 611 TGC to TTC (exon 10) in the RET proto-oncogene leading to a replacement of cysteine by phenylalanine (Cys611Phe or C611F). RESULTS: Twenty family members of this large kindred are gene carriers (GCs) and seven (5-13 years old) are potential carriers but have yet to be analysed. The clinical course of medullary thyroid carcinoma (MTC) in this family is characterized by a very slow evolution and progression of the tumour with no MTC-related death to date. Of 11 patients (30-69 years old) having undergone thyroidectomy six were classified as pT1, four as pT2 and one as C-cell hyperplasia according to the TNM system of the International Union Against Cancer. Due to cervical and mediastinal lymph node metastasis one patient (44 years old) had to be operated on a second time. The seven non-operated GCs of the fourth and fifth generation (17-26 years old) are yearly monitored with pentagastrin stimulation tests; one non-operated GC (43 years old) has refused any further investigations. Screening for primary hyperparathyroidism and phaeochromocytoma was negative in all cases. CONCLUSION: We suggest from these experiences that the general advice for thyroidectomy in early childhood should be modified in certain families, depending on genotype.

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxicity is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calcium-binding astroglial key protein S100β is released in response to glial activation, and its measurement in serum only recently became possible. Serum S100β was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shunt. Subclinical portal-systemic encephalopathy and overt portal-systemic encephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100β was specifically elevated in the presence of subclinical or early portal-systemic encephalopathy, but not arterial ammonia. S100β levels elevated above a reference value (S100β ≤ 110pg/ml) or the cut off value determined in our group of patients (112pg/ml) predicted subclinical portal-systemic encephalopathy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100β was significantly dependent on liver dysfunction (Child-Pugh score), but was more closely related to cognitive impairments than the score. Serum S100β seems to be a promising biochemical surrogate marker for mild cognitive impairments due to portal-systemic encephalopathy.

Background/Aims: Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirhrosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. Methods: Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. Results: Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with control group ( p =0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p =0.02). Conclusions: Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.

This paper focuses on psychiatric aspects of portal-systemic encephalopathy (PSE) due to chronic liver disease and/or portal-systemic shunting. Clinical syndromes of PSE are discussed from the point of view of biological psychiatry, but, psychological consequences of concomitant cognitive disorders are also addressed. Psychiatric symptoms of early PSE and sleep disorders in patients with chronic liver disease are of specific interest.

The Budd-Chiari syndrome is one cause of portal hypertension with multiple etiology and different therapeutic interventional strategies. We report on a 23-year-old female patient who developed de novo liver tumors 33 months after portocaval shunting for acute Budd-Chiari syndrome.

The effect of GH substitution on serum lipids and lipoproteins, and in particular lipoprotein(a) (Lp(a)), was investigated in 32 adults with postoperative (acquired) GH deficiency as part of a double-blind, placebo-controlled trial. Seventeen men and fifteen women, aged 18-59 years (mean 42 years) from two centres (Hannover and Gottingen) were randomly assigned to two groups. Group P (placebo) received placebo for the first 12 months and recombinant human GH (rhGH) for the following 12 months (open phase). Group V (verum) was treated with rhGH for two consecutive periods of 12 months each. The target dose of rhGH was 2 U/m2 per day, given subcutaneously daily at bedtime. Serum concentrations of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were determined at 0, 12 and 24 months. In group V, Lp(a) increased significantly in the first as well as in the second year of treatment (P=0.02, 12 months versus baseline; P=0.016, 24 months versus 12 months). In contrast, Lp(a) levels remained unchanged in group P during the first 12 months (P=0.826 versus baseline), but increased significantly (P=0.002) during the second year, when all patients were administered GH. The increase in Lp(a) after 12 months of rhGH replacement therapy in all 32 patients was significant for Lp(a) baseline concentrations both above and below 20 mg/dl and was independent of the apolipoprotein(a) isoforms. Total and LDL-C decreased significantly after 1 year and triglycerides after 2 years in group V. A significant reduction was also observed in the TC/HDL-C and the LDL-C/HDL-C ratios. Our study shows an unfavorable effect of rhGH replacement therapy on Lp(a) levels, which is, however, counteracted by a favorable effect of rhGH on TC, LDL-C and the TC/LDL-C and LDL-C/HDL-C ratios.

Background—Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6Chigh monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E–deficient (apoE−/−) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset–targeted RNAi altered infarct inflammation and healing. Methods and Results—Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE−/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18–labeled positron emission tomography agent (18F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P, National Heart, Lung, and Blood Institute, United States. Dept. of Health and Human Services (contract No. HHSN268201000044C), National Institutes of Health (U.S.) (grant R01-HL096576), National Institutes of Health (U.S.) (grant R01-HL095629), National Institutes of Health (U.S.) (grant T32-HL094301), Deutsche Forschungsgemeinschaft (HE-6382/1-1)

This study aims to characterize the effect of background tissue density and heterogeneity on the detection of irregular masses in breast tomosynthesis, while demonstrating the capability of the sophisticated tools that can be used in the design, implementation, and performance analysis of virtual clinical trials (VCTs). Twenty breast phantoms from the extended cardiac-torso (XCAT) family, generated based on dedicated breast computed tomography of human subjects, were used to extract a total of 2173 volumes of interest (VOIs) from simulated tomosynthesis images. Five different lesions, modeled after human subject tomosynthesis images, were embedded in the breasts and combined with the lesion absent condition yielded a total of [Formula: see text] VOIs. Effects of background tissue density and heterogeneity on the detection of the lesions were studied by implementing a composite hypothesis signal detection paradigm with location known exactly, lesion known exactly or statistically, and background known statistically. Using the area under the receiver operating characteristic curve, detection performance deteriorated as density was increased, yielding findings consistent with clinical studies. A human observer study was performed on a subset of the simulated tomosynthesis images, confirming the detection performance trends with respect to density and serving as a validation of the implemented detector. Performance of the implemented detector varied substantially across the 20 breasts. Furthermore, background tissue density and heterogeneity affected the log-likelihood ratio test statistic differently under lesion absent and lesion present conditions. Therefore, considering background tissue variability in tissue models can change the outcomes of a VCT and is hence of crucial importance. The XCAT breast phantoms have the potential to address this concern by offering realistic modeling of background tissue variability based on a wide range of human subjects, comprising various breast shapes, sizes, and densities.

The aim of this study was to evaluate the benefits and limitations of using three dimensional (3D) musculoskeletal modelling (LifeModeler) in assessing the safety and efficacy of exercising on an abdominal crunch resistance training machine. Three anthropometric cases were studied, representing a 5th percentile female, and 50th percentile and 95th percentile male. Results indicated that the LifeModeler default model was capable of solving the forward dynamics simulations without adjustments. The modelling was able to indicate high risk for back injury when performing the abdominal crunch exercise as a result of the unacceptable intervertebral joint loading that occurs during the exercise. Individuals with small anthropometric dimensions such as some females and children cannot be accommodated suitably on the abdominal crunch machine which negatively impacts exercise posture and technique. Hip flexor muscle contribution in the execution of the exercise for the 5th percentile female was substantial thus reducing the efficacy of the exercise in isolating the abdominal muscles.

Mammography is currently the most widely accepted tool for detection and diagnosis of breast cancer. However, the sensitivity of mammography is reduced in women with dense breast tissue due to tissue overlap, which may obscure lesions. Digital breast tomosynthesis with contrast enhancement reduces tissue overlap and provides additional functional information about lesions (i.e. morphology and kinetics), which in turn may improve lesion characterization. The performance of such techniques is highly dependent on the structural composition of the breast, which varies significantly across patients. Therefore, optimization of breast imaging systems should be done with respect to this patient versatility. Furthermore, imaging techniques that employ contrast require the inclusion of a temporally varying breast composition with respect to the contrast agent kinetics to enable the optimization of the system. To these ends, we have developed a dynamic 4D anthropomorphic breast phantom, which can be used for optimizing a breast imaging system by incorporating material characteristics. The presented dynamic phantom is based on two recently developed anthropomorphic breast phantoms, which can be representative of a whole population through their randomized anatomical feature generation and various compression levels. The 4D dynamic phantom is incorporated with the kinetics of contrast agent uptake in different tissues and can realistically model benign and malignant lesions. To demonstrate the utility of the proposed dynamic phantom, contrast-enhanced digital mammography and breast tomosynthesis were simulated where a ray-tracing algorithm emulated the projections, a filtered back projection algorithm was used for reconstruction, and dual-energy and temporal subtractions were performed and compared.

One major hallmark of Alzheimer's disease (AD) is the massive loss of synapses that occurs at an early clinical stage of the disease. In this study, we characterize alterations in spine density and the expression of synapse-associated immediate early gene Arc (activity-regulated cytoskeleton-associated protein) in the hippocampal CA1 regions of two different amyloid precursor protein (APP) transgenic mouse lines before plaque development and their connection to performance in hippocampus-dependent memory tests. The density of mushroom-type spines was reduced by 34% in the basal dendrites proximal to the soma of CA1 pyramidal neurons in 5.5-month-old Tg2576 mice, carrying the Swedish mutation, compared with wild-type littermates. A similar reduction of 42% was confirmed in the same region of 8-month-old APP/Lo mice, carrying the London mutation. In this strain, the reduction extended to the distal dendritic spines (28%), although no differences were found in apical dendrites in either transgenic mouse line. Both transgenic mice lines presented a significant increase in Arc protein expression in CA1 compared with controls, suggesting rather an overactivity and increased spine turnover that was supported by a significant decrease in number of somatostatin-immunopositive inhibitory interneurons in the stratum oriens of CA1. Behaviorally, the transgenic mice showed decrease freezing in the fear contextual conditioning test and impairment in spatial memory assessed by Morris water maze test. These data indicate that cognitive impairment in APP transgenic mice is correlated with impairment of synaptic connectivity in hippocampal CA1, probably attributable to loss of inhibitory interneurons and subsequent hyperactivity.

Introduction: Opportunities to determine optimal rates of fluid ingestion could reduce the mass soldiers might need to carry on military missions. Purpose: The first objective was to evaluate the effects of an ad libitum fluid replacement strategy on total body water (TBW), core temperature, serum sodium concentrations [Na+], and plasma osmolality (POsm). The second objective was to determine if an ad libitum water intake was sufficient to maintain these variables during exercise. A third objective was to determine if changes in body mass are an accurate measure of changes in TBW. Methods: A field study was conducted with 15 soldiers performing a 16.4-km route march. The average age of 15 subjects was 27 yr (SD = 4.6 yr). Results: Their mean hourly ad libitum fluid intake was 383 mL (SD = 150 mL). Predicted sweat rate was 626 ± 122 mL·h-1. Despite an average body mass loss of 1.0 kg (SD = 0.50 kg) TBW, POsm and serum [Na+] did not change significantly during exercise. There was a significant (P < 0.05) linear relationship with a negative slope between postexercise serum [Na+] and changes in both body mass and percentage of TBW. Postexercise POsm and serum [Na+] were significantly related (P < 0.05). Higher postexercise percentage of TBW was associated with lower postexercise POsm and serum [Na+] levels. There was no relation between percent body mass loss and postexercise core temperature (38.1°C ± 0.6°C). Conclusions: A mean ad libitum water intake of 383 mL·h-1, replacing approximately 61% of body mass losses during 4 h of exercise, maintained TBW, core temperature, POsm, and serum [Na+] despite a 1.4% body mass loss. A reduction in body mass of 1.4% (1.0 kg) was not associated with a reduction in TBW.

reduced (ps 0.05) in the 33, 54, and 62 week APP/PS1 animals as compared to age-matched PS1 animals. The perfusion reduction was also observed in 8 week old animals but genotype effect just failed to reach statistical significance at this age (p 0.0505). Hypoperfusion was detected in the medial posterior cortex of the 33 and 62 week old APP/PS1 (p 0.01). A trend for hypoperfusion was noted in the 54 week old animals but was not statistically significant (p 0.06). At the level of the thalamus, hypoperfusion, was only seen in 8 week old APP/PS1 mice (p 0.05). Conclusions: Our longitudinal study showed a hypoperfusion in cortical regions from APP/PS1 mice. As perfusion can be measured non-invasively both in humans and animals, it might be used as a translational marker to follow drug effects both in animals and humans. Acknowledgments: Sanofi-Aventis Neurodegenerative Disease Group for the gift of the animals, French ‘Federation-for-Brain-Research’, ‘Neuroscience-ACI-programs’ French Ministry of Research.

Current mammographic screening for breast cancer is less effective for younger women. To complement mammography for premenopausal women, we investigated the feasibility screening test using 98 blood serum proteins. Because the data set was very noisy and contained only weak features, we used a classifier designed for noisy data: decision fusion. Decision fusion outperformed both a support vector machine (SVM) and linear regression with forward stepwise feature selection on all three two-class classification tasks: normal tissue vs. cancer, normal tissue vs. benign lesions, and benign lesions vs. cancer. Decision fusion detected cancer moderately well (AUC=0.84 on normal vs. cancer), demonstrating promise as a screening tool. Decision fusion also detected benign lesions similarly well (AUC=0.83 on normal vs. benign lesions) and was the only classifier to achieve any success in separating benign from malignant lesions (AUC=0.64 on benign vs. cancer). The classification results suggest that the assayed proteins are more indicative of a secondary effect, such as immune response, rather than specific for breast cancer. In conclusion, the decision fusion classifier demonstrated some promise in detecting breast lesions and outperformed other classifiers, especially for the very noisy classification problem of distinguishing benign from malignant lesions.

Background Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). Methods Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). Results Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. Conclusion In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.

Objective Patients with non-resectable liver metastases of colorectal cancer have poor prognosis and are mainly treated by palliative chemotherapy. Laser interstitial thermo-therapy is an innovative minimal invasive procedure for local tumour destruction within solid organs. The aim of the study was to investigate quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy (US-LITT) in patients with liver metastases of colorectal cancer. Methods In this prospective non-randomized study, 45 patients with liver metastases of colorectal cancer were palliatively treated by US-LITT. Patient survival was analysed by the Kaplan–Meier method and the quality of life by questionnaire C30 of the European Organisation for Research and Treatment of Cancer before, and 1 week, 1 month, and 6 months after initiation of US-LITT. Results Median survival after initiation of US-LITT was 8.5 ± 0.7 months with a range of 1.5–18 months. Body weight was constant 1 month after US-LITT. In the multivariate analyses, quality-of-life symptoms and functioning scales did not deteriorate in patients alive at 6 months after initiation of US-LITT. Univariate analyses outlined a significant increase of the pain subscale before and at 1 week after US-LITT. Conclusions This study first describes the quality of life in patients with liver metastases of colorectal cancer treated by US-LITT. Potential benefits of the minimal invasive procedure could be prolonged survival time by preserved quality of life, but this first impression needs to be verified in a comparative study.

Background: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic stent-shunts (TIPS). Methods: Glucagon, plasma glucose, HbA1c, C-peptide and insulin were determined in peripheral venous samples from 21 diabetic (D)- and 15 non-diabetic patients (ND; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with comparable clinical features (age, BMI, Child-Pugh-score, creatinine) before, 3 and 9 months after TIPS implantation. Results: Glucogon levels before TIPS were elevated in diabetics compared to non-diabetics (D: 145,4±52,1 vs. ND: 97,3±49,8 pg/ml; p=0,057). Three and nine months after TIPS implantation glucagon levels increased significantly in ND (183,9±80,3 and 176,2±93,4 pg/ml) but not in D (169,0±62,4 and 171,9±58,4 pg/ml). While plasma glucose, HbA1c and C-peptide were significantly higher in D than in ND, they did not change significantly three and nine months after TIPS implantation. Insulin was increased in D before TIPS (D: 31,8±15,9 vs. ND: 14,8±7,1 mU/l; p=0,0001). Three and nine months after TIPS insulin significantly increased in ND (26,6±14,7 and 23,2±10,9 vs. 14,8±7,1 mU/l before TIPS) but not in D. Liver and kidney function did not change with time. Conclusions: In non-diabetic cirrhotic patients TIPS implantation is followed by a significant increase of plasma glucagon. However this does not result in a worsening of glycemic control, apparently because of a simultaneous increase of insulin.