Soliton-induced relativistic-scattering and amplification.

Solitons are of fundamental importance in photonics due to applications in optical data transmission and also as a tool for investigating novel phenomena ranging from light generation at new frequencies and wave-trapping to rogue waves. Solitons are also moving scatterers: they generate refractive index perturbations moving at the speed of light. Here we found that such perturbations scatter light in an unusual way: they amplify light by the mixing of positive and negative frequencies, as we describe using a first Born approximation and numerical simulations. The simplest scenario in which these effects may be observed is within the initial stages of optical soliton propagation: a steep shock front develops that may efficiently scatter a second, weaker probe pulse into relatively intense positive and negative frequency modes with amplification at the expense of the soliton. Our results show a novel all-optical amplification scheme that relies on soliton induced scattering.

Negative-frequency resonant radiation.

Optical solitons or solitonlike states shed light to blueshifted frequencies through a resonant emission process. We predict a mechanism by which a second propagating mode is generated. This mode, called negative resonant radiation, originates from the coupling of the soliton mode to the negative-frequency branch of the dispersion relation. Measurements in both bulk media and photonic-crystal fibers confirm our predictions.

Evolution of light trapped by a soliton in a microstructured fiber.

We observe the dynamics of pulse trapping in a microstructured fiber. Few-cycle pulses create a system of two pulses: a Raman shifting soliton traps a pulse in the normal dispersion regime. When the soliton approaches a wavelength of zero group velocity dispersion the Raman shifting abruptly terminates and the trapped pulse is released. In particular, the trap is less than 4 ps long and contains a 1 ps pulse. After being released, this pulse asymmetrically expands to more than 10 ps. Additionally, there is no disturbance of the trapping dynamics at high input pulse energies as the supercontinuum develops further.

Measuring the effect of a study meal on portal concentrations of glucagon-like peptide 1 (GLP-1) in non diabetic and diabetic patients with liver cirrhosis: transjugular intrahepatic portosystemic stent shunt (TIPSS) as a new method for metabolic measurements.

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.

TIPS implantation raises leptin levels in patients with liver cirrhosis.

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.

Ultrasound-guided laser interstitial thermo therapy for treatment of non-resectable primary and secondary liver tumours--a feasibility study.

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.

Ultrasound imaging of Nd:YAG laser-induced tissue coagulation in porcine livers.

AIMS: Absorption of laser light energy induces denaturation of proteins and thermocoagulation of irradiated tissue. Recently, MRI-guided laser coagulation in combination with MR thermometry was reported as a treatment of liver tumours. In the present study ultrasonographic imaging was evaluated for its suitability in laser induced tissue thermocoagulation. METHODS: Fresh porcine livers were used for ex vivo examinations. Placement of the laser catheter and tissue coagulation during laser light emission were online monitored by ultrasonography. Nd:YAG laser-induced tissue damage was evaluated by macroscopical and microscopical examinations of histological sections. RESULTS: During laser light emission a marked hyperdense signal enhancement was observed by ultrasonography which strongly correlated with the extent of macroscopic tissue damage. The size of laser-induced coagulation zone depended on both the power setting and total energy delivered. Carbonization of the tissue surrounding the laser tip is a limiting factor because of laser light absorption. However our data indicate that using appropriate laser energy and exposure time prevent carbonization although carbonization can not be visualized by ultrasonography. CONCLUSIONS: It is concluded from the present ex vivo studies that laser coagulation can be effectively performed under ultrasonographic guidance.

Relativistic effects of light in moving media with extremely low group velocity

A moving dielectric medium acts as an effective gravitational field on light. One can use media with extremely low group velocities [Lene Vestergaard Hau et al., Nature (London) 397, 594 (1999)] to create dielectric analogs of astronomical effects on Earth. In particular, a vortex flow imprints a long-ranging topological effect on incident light and can behave like an optical black hole.

Serum procalcitonin and proinflammatory cytokines in a patient with acute severe leptospirosis.

Leptospirosis is a zoonosis, with clinical manifestations ranging from the imperceptible to severe, potentially fatal renal and liver failure accompanied by haemorrhage and jaundice. In this case report of a patient with severe leptospirosis, serum levels of procalcitonin decreased ahead of any obvious clinical improvement, and thus may be useful as a prognostic marker. Levels of soluble IL-2 receptor were very high and correlated well with the clinical course.

Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism.

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Circulating human hepatic lipase mRNA in patients with hepatocellular carcinoma and healthy controls.

OBJECTIVE: To evaluate circulating human hepatic lipase mRNA as an indicator of circulating hepatoma cells by reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with hepatocellular carcinoma (HCC). DESIGN: Prospective study SETTING: University hospital, Germany. SUBJECTS: 15 patients with hepatocellular carcinoma and 8 healthy volunteers. INTERVENTIONS: Peripheral venous blood was obtained and total RNA was extracted from the lymphocytic layer by caesium chloride gradient centrifugation. The mRNA was reverse transcripted, and hepatic lipase cDNA was amplified by hepatic lipase specific primers with PCR. The integrity of isolated RNA was confirmed by RT-PCR with beta-actin specific primers. Amplificates were visualised by agarose gel electrophoresis and ethidium bromide staining. MAIN OUTCOME MEASURES: Detection of hepatic-lipase-specific RT-PCR products in peripheral blood. RESULTS: Circulating hepatic lipase-specific PCR products were detected in all patients with HCC and in all healthy controls. CONCLUSION: Detection of circulating human hepatic lipase-mRNA by RT-PCR does not indicate metastasising HCC.

A synthetic glucagon-like peptide-1 analog with improved plasma stability.

Glucagon-like peptide-1 (GLP-1) is the most potent endogenous insulin-stimulating hormone. In the present study the plasma stability and biological activity of a GLP-1 analog, [Ser]GLP-1(7-36)amide, in which the second N-terminal amino acid alanine was replaced by serine, was evaluated in vitro and in vivo. Incubation of GLP-1 with human or rat plasma resulted in degradation of native GLP-1(7-36)amide to GLP-1(9-36)amide, while [Ser]GLP-1(7-36)amide was not significantly degraded by plasma enzymes. Using glucose-responsive HIT-T15 cells, [Ser]GLP-1(7-36)amide showed strong insulinotropic activity, which was inhibited by the specific GLP-1 receptor antagonist exendin-4(9-39)amide. Simultaneous i.v. injection of [Ser]GLP-1(7-36)amide and glucose in rats induced a twofold higher increase in plasma insulin levels than unmodified GLP-1(7-36)amide with glucose and a fivefold higher increase than glucose alone. [Ser]GLP-1(7-36)amide induced a 1.5-fold higher increase in plasma insulin than GLP-1(7-36)amide when given 1 h before i.v. application of glucose. The insulinotropic effect of [Ser]GLP-1(7-36)amide was suppressed by i.v. application of exendin-4(9-39)amide. The present data demonstrate that replacement of the second N-terminal amino acid alanine by serine improves the plasma stability of GLP-1(7-36)amide. The insulinotropic action in vitro and in vivo was not impaired significantly by this modification.

[Doppler sonographic short- and long-term studies of portal hemodynamics following transjugular intrahepatic portasystemic shunt (TIPSS)]. / Doppler-sonographische Kurz- und Langzeit-untersuchungen der portalen Hämodynamik nach transjugulärem intrahepatischem portosystemischem Stent-Shunt (TIPS).

Shunt insufficiency due to shunt occlusion or stenosis is frequent after TIPS (about 50% after one year). Controversially discussed is whether Doppler sonography is effective in detecting shunt stenosis or whether regular angiographies are required. The experience with a noninvasive method of surveillance primarily based on Doppler sonography is reported here. 58 patients (35 men, 23 women, mean age 55 years, range 33-82 years) were treated by TIPS because of complications of portal hypertension (43 x gastroesophageal bleeding, 14 x refractory ascites, 1 x venoocclusive disease). Liver cirrhosis (alcoholtoxic etiology in 63%) was present in 55 cases, according to Child-Pugh's classification 23 patients = A, 19 patients = B and 13 patients = C. Within a mean observation period of 14 months, Doppler sonography was performed in three months intervals, endoscopy in six months intervals and angiography only when shunt insufficiency was suspected by Doppler sonography and/or because of clinical events, e.g. recurrent bleeding. Immediately after TIPS, maximal flow velocity and flow volume in the portal vein increased by 116% and 115%, respectively. Three months later, a significant increase of portal vein diameter of about 15% was measured. Shunt flow was initially 2.700 ml/min (one week after TIPS) and decreased progressively by about 30% within the first nine months of follow-up. Correspondingly, angiographically proven shunt insufficiency was present in 22 patients (33 episodes). A total of twelve bleeding episodes recurred in seven patients (rebleeding rate of 16% after one year and 19% after two years). In the remaining 15 patients (68%; 21 episodes) shunt insufficiency could be corrected prior to complications because of detection by Doppler sonography (19x) and endoscopy (2x). Therefore, Doppler sonography is an effective diagnostic tool for the detection of shunt insufficiency and should be performed at three months intervals for at least 18 months. In this context it appears allowable to avoid routine angiographies.

Serum leptin levels in hypo- and hyperthyroidism.

Leptin, the product of the ob gene, is an important circulating signal for the regulation of body weight. In the present study the role of immunoreactive leptin (leptin-IR) was investigated in functional thyroid disease. Serum leptin-IR levels of 23 hypothyroid and 19 hyperthyroid patients were compared with 21 controls. Leptin-IR was quantified by a specific RIA. In hyperthyroid patients, leptin-IR was not different from controls. Serum leptin-IR levels were significantly increased in hypothyroid patients (21.0 +/- 2.7 micrograms/l vs controls 10.8 +/- 2.1 micrograms/l, P = 0.0044). When serum leptin of hypothyroid patients was compared with euthyroid controls of the same body mass index the difference was still significant (P = 0.0333 by paired Student's t-test). This might indicate that elevation of the serum leptin level does not merely reflect changes in body weight secondary to hypothyroidism, but might be increased to overcome the gain of body weight caused by hypothyroidism.

Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite.

Patients with craniopharyngioma frequently suffer from severe obesity. Leptin induces an inhibition of appetite via hypothalamic receptors. This study was undertaken to investigate whether a relationship exists between serum leptin levels and pituitary/hypothalamic lesions in craniopharyngioma patients. Serum leptin levels were evaluated by RIA in 14 patients (age 7-21 years; 7 females, 7 males) after they had undergone neurosurgical treatment for craniopharyngioma. Normal controls had a positive correlation between leptin levels and body mass index (BMI) with higher levels in the females than in the males. Significantly elevated leptin levels with respect to BMI were found in 11 craniopharyngioma patients who had been affected by a suprasellar tumour, whereas 3 patients with an intrasellar tumour had lower, almost normal serum leptin levels. Our data suggest that craniopharyngioma patients develop hypothalamic obesity because their hypothalamic structures are insensitive to endogenous leptin. The elevated serum leptin concentrations found only in patients with a suprasellar tumour may be explained by a disturbed feedback mechanism from the hypothalamic leptin receptors to the adipose tissue.

Release of glucagon-like peptide-1 (GLP-1) by carbohydrates in the perfused rat ileum.

The effect of various carbohydrates on glucagon-like peptide-1 (GLP-1) release was studied in the in vivo perfused rat ileum. GLP-1 concentrations in the mesenteric venous effluent increased significantly after luminal perfusion with substrates of a sodium/glucose co-transporter (D-glucose, D-galactose, methyl-alpha D-glucoside, and 3-O-methyl-D-glucose). D-Fructose induced a sodium-independent release of GLP-1. Carbohydrates like 2-deoxy-D-glucose and N-acetyl-D-glucosamine, which are not substrates of a luminal sodium/glucose or fructose transporter, did not affect GLP-1 release. Since methyl-alpha D-glucoside is not a substrate of the basolateral glucose transport mechanism and 3-O-methyl-D-glucose is not metabolized within intestinal cells, it is concluded that intracellular metabolism of carbohydrates and intracellular removal are not essential to induce GLP-1 secretion in rats.

Detection of circulating albumin-mRNA by RT-PCR does not indicate metastasizing hepatocellular carcinoma.

Hepatocellular carcinomas (HCC) frequently recur after partial liver resection or orthotopic liver transplantation, possibly because of the presence of a small number of hepatoma cells in the peripheral blood. Detection of circulating HCC cells might improve therapeutic options and could predict disease recurrence resulting from a metastasizing disease. In the present study, human albumin-mRNA was detected by RT-PCR in the peripheral blood of patients with hepatocellular carcinoma. Circulating albumin-specific PCR products were detected in each patient with HCC, but also in healthy volunteers. It is concluded that albumin-mRNA is not specific to circulating hepatoma cells and therefore does not indicate metastasizing disease.